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Consider a scenario where a novel neuromuscular blocking agent, 'Curariform X,' is developed, exhibiting a unique mechanism of action distinct from known paralytics. Instead of directly competing with acetylcholine (ACh) at the nicotinic receptor, 'Curariform X' allosterically modulates the receptor's conformation, preventing ion channel opening even when ACh is bound. Furthermore, it exhibits a high degree of selectivity for specific subtypes of nicotinic receptors found predominantly at the neuromuscular junction of fast-twitch muscle fibers. In a series of in vitro experiments, it is observed that 'Curariform X' significantly reduces the amplitude of end-plate potentials (EPPs) in these muscle fibers. Given this information, which of the following observations would most strongly support the hypothesis that 'Curariform X' exerts its paralytic effect primarily through its allosteric modulation of the nicotinic acetylcholine receptor?
Consider a scenario where a novel neuromuscular blocking agent, 'Curariform X,' is developed, exhibiting a unique mechanism of action distinct from known paralytics. Instead of directly competing with acetylcholine (ACh) at the nicotinic receptor, 'Curariform X' allosterically modulates the receptor's conformation, preventing ion channel opening even when ACh is bound. Furthermore, it exhibits a high degree of selectivity for specific subtypes of nicotinic receptors found predominantly at the neuromuscular junction of fast-twitch muscle fibers. In a series of in vitro experiments, it is observed that 'Curariform X' significantly reduces the amplitude of end-plate potentials (EPPs) in these muscle fibers. Given this information, which of the following observations would most strongly support the hypothesis that 'Curariform X' exerts its paralytic effect primarily through its allosteric modulation of the nicotinic acetylcholine receptor?
- Reversal of paralysis by increasing the concentration of calcium ions in the extracellular fluid.
- A concentration-dependent decrease in the binding affinity of acetylcholine to the nicotinic receptor in the presence of 'Curariform X,' without affecting the maximal number of binding sites. (correct)
- Enhancement of the paralytic effect of 'Curariform X' by acetylcholinesterase inhibitors.
- Increased levels of acetylcholine in the synaptic cleft following administration of 'Curariform X.'
A graduate student is investigating the effects of varying stimulation frequencies on skeletal muscle contraction. They observe that at low stimulation frequencies (e.g., 10 Hz), the muscle exhibits distinct twitches with complete relaxation between stimuli. However, as the stimulation frequency is progressively increased (e.g., to 50 Hz), the individual twitches begin to summate, resulting in a sustained increase in muscle tension. At even higher frequencies (e.g., 100 Hz), the muscle reaches a state of maximal tension, with no discernible relaxation between stimuli. Considering the physiological mechanisms underlying these observations, what is the most accurate explanation for the transition from unfused tetanus to fused tetanus as the stimulation frequency increases?
A graduate student is investigating the effects of varying stimulation frequencies on skeletal muscle contraction. They observe that at low stimulation frequencies (e.g., 10 Hz), the muscle exhibits distinct twitches with complete relaxation between stimuli. However, as the stimulation frequency is progressively increased (e.g., to 50 Hz), the individual twitches begin to summate, resulting in a sustained increase in muscle tension. At even higher frequencies (e.g., 100 Hz), the muscle reaches a state of maximal tension, with no discernible relaxation between stimuli. Considering the physiological mechanisms underlying these observations, what is the most accurate explanation for the transition from unfused tetanus to fused tetanus as the stimulation frequency increases?
- Insufficient time for complete removal of calcium ions from the sarcoplasm between successive stimuli, leading to a sustained saturation of troponin and continuous exposure of myosin-binding sites on actin. (correct)
- The summation of individual muscle fiber action potentials, resulting in a sustained depolarization of the sarcolemma and prolonged activation of voltage-gated calcium channels.
- Progressive depletion of ATP, leading to a reduction in the rate of cross-bridge cycling and a sustained increase in muscle tension.
- Increased efficiency of calcium reuptake into the sarcoplasmic reticulum, resulting in a sustained elevation of intracellular calcium concentration and continuous cross-bridge formation.
In a groundbreaking study, researchers have discovered a novel protein, 'MyoRestin,' expressed exclusively in skeletal muscle cells. 'MyoRestin' is found to interact directly with the ryanodine receptor (RyR1) on the sarcoplasmic reticulum (SR), modulating its calcium release properties. Further investigation reveals that phosphorylation of 'MyoRestin' by protein kinase A (PKA) significantly enhances its inhibitory effect on RyR1, reducing calcium release in response to a given stimulus. Based on these findings, which of the following scenarios would most likely occur in skeletal muscle cells expressing a constitutively active, non-phosphorylatable mutant of 'MyoRestin'?
In a groundbreaking study, researchers have discovered a novel protein, 'MyoRestin,' expressed exclusively in skeletal muscle cells. 'MyoRestin' is found to interact directly with the ryanodine receptor (RyR1) on the sarcoplasmic reticulum (SR), modulating its calcium release properties. Further investigation reveals that phosphorylation of 'MyoRestin' by protein kinase A (PKA) significantly enhances its inhibitory effect on RyR1, reducing calcium release in response to a given stimulus. Based on these findings, which of the following scenarios would most likely occur in skeletal muscle cells expressing a constitutively active, non-phosphorylatable mutant of 'MyoRestin'?
- Increased muscle contractility but decreased resistance to fatigue due to impaired calcium reuptake.
- Decreased muscle contractility and increased susceptibility to fatigue due to reduced calcium release. (correct)
- No significant change in muscle contractility or fatigue resistance due to compensatory mechanisms.
- Enhanced muscle contractility and increased resistance to fatigue due to increased calcium release.
Researchers are investigating the effects of a novel compound, 'Sarcolax,' on skeletal muscle relaxation. They discover that 'Sarcolax' selectively inhibits the activity of the SERCA pump in skeletal muscle cells. Which of the following downstream effects would most likely be observed in these cells following exposure to 'Sarcolax'?
Researchers are investigating the effects of a novel compound, 'Sarcolax,' on skeletal muscle relaxation. They discover that 'Sarcolax' selectively inhibits the activity of the SERCA pump in skeletal muscle cells. Which of the following downstream effects would most likely be observed in these cells following exposure to 'Sarcolax'?
A team of scientists discovers a new variant of myosin heavy chain protein (MyHC-X) in a population of elite sprinters. This variant exhibits a unique ATP hydrolysis rate that is significantly faster than that of the 'wild-type' MyHC found in the general population. Assuming all other factors are equal, which of the following biophysical properties would most likely characterize the muscle fibers expressing MyHC-X?
A team of scientists discovers a new variant of myosin heavy chain protein (MyHC-X) in a population of elite sprinters. This variant exhibits a unique ATP hydrolysis rate that is significantly faster than that of the 'wild-type' MyHC found in the general population. Assuming all other factors are equal, which of the following biophysical properties would most likely characterize the muscle fibers expressing MyHC-X?
Consider a scenario where a mutation in the gene encoding for titin results in a significantly shorter titin protein within skeletal muscle sarcomeres. Assuming that the expression levels of all other sarcomeric proteins remain unchanged, which of the following structural and functional alterations would most likely occur in the affected muscle fibers?
Consider a scenario where a mutation in the gene encoding for titin results in a significantly shorter titin protein within skeletal muscle sarcomeres. Assuming that the expression levels of all other sarcomeric proteins remain unchanged, which of the following structural and functional alterations would most likely occur in the affected muscle fibers?
A novel myotoxin, 'Necrotoxin-A,' is discovered to selectively target and disrupt the structural integrity of the sarcolemma in skeletal muscle fibers. 'Necrotoxin-A' induces the formation of large, non-selective pores in the sarcolemma, leading to a loss of membrane potential and uncontrolled influx of extracellular calcium. Which of the following pathological consequences would most likely arise as a direct result of 'Necrotoxin-A' exposure?
A novel myotoxin, 'Necrotoxin-A,' is discovered to selectively target and disrupt the structural integrity of the sarcolemma in skeletal muscle fibers. 'Necrotoxin-A' induces the formation of large, non-selective pores in the sarcolemma, leading to a loss of membrane potential and uncontrolled influx of extracellular calcium. Which of the following pathological consequences would most likely arise as a direct result of 'Necrotoxin-A' exposure?
In a study examining the effects of chronic exercise on skeletal muscle plasticity, researchers observe a significant shift in the proportion of different myosin heavy chain (MyHC) isoforms in the muscles of endurance-trained athletes. Specifically, they find a marked increase in the expression of MyHC I and a corresponding decrease in MyHC IIx isoforms. Which of the following metabolic and functional adaptations would most likely accompany this shift in MyHC isoform expression?
In a study examining the effects of chronic exercise on skeletal muscle plasticity, researchers observe a significant shift in the proportion of different myosin heavy chain (MyHC) isoforms in the muscles of endurance-trained athletes. Specifically, they find a marked increase in the expression of MyHC I and a corresponding decrease in MyHC IIx isoforms. Which of the following metabolic and functional adaptations would most likely accompany this shift in MyHC isoform expression?
Researchers discover a novel signaling pathway in skeletal muscle cells that regulates the expression of genes involved in mitochondrial biogenesis. This pathway is activated by a specific microRNA, 'miR-X,' which is upregulated in response to endurance exercise. 'miR-X' directly targets and inhibits the translation of a transcriptional repressor, 'Restin,' which normally suppresses the expression of PGC-1α, a master regulator of mitochondrial biogenesis. Based on these findings, which of the following interventions would most likely enhance mitochondrial biogenesis in skeletal muscle cells?
Researchers discover a novel signaling pathway in skeletal muscle cells that regulates the expression of genes involved in mitochondrial biogenesis. This pathway is activated by a specific microRNA, 'miR-X,' which is upregulated in response to endurance exercise. 'miR-X' directly targets and inhibits the translation of a transcriptional repressor, 'Restin,' which normally suppresses the expression of PGC-1α, a master regulator of mitochondrial biogenesis. Based on these findings, which of the following interventions would most likely enhance mitochondrial biogenesis in skeletal muscle cells?
A researcher is investigating the effects of different extracellular calcium concentrations on the force-frequency relationship in isolated skeletal muscle fibers. They observe that at very low extracellular calcium concentrations (e.g., 0.5 mM), the muscle fibers exhibit a significant reduction in maximal force production, even at high stimulation frequencies. Which of the following mechanisms is the most likely explanation for this observation?
A researcher is investigating the effects of different extracellular calcium concentrations on the force-frequency relationship in isolated skeletal muscle fibers. They observe that at very low extracellular calcium concentrations (e.g., 0.5 mM), the muscle fibers exhibit a significant reduction in maximal force production, even at high stimulation frequencies. Which of the following mechanisms is the most likely explanation for this observation?
A team of bioengineers is designing an artificial muscle construct for implantation in patients with severe muscle atrophy. They are considering different biomaterials and cell types for this construct. Which of the following design parameters would be most critical for ensuring the long-term functional integration and performance of the artificial muscle in vivo?
A team of bioengineers is designing an artificial muscle construct for implantation in patients with severe muscle atrophy. They are considering different biomaterials and cell types for this construct. Which of the following design parameters would be most critical for ensuring the long-term functional integration and performance of the artificial muscle in vivo?
A research team discovers a novel post-translational modification on troponin I (TnI) that selectively alters its interaction with tropomyosin. This modification, termed 'Phospho-Inhibition,' occurs specifically at a serine residue located near the C-terminus of TnI and enhances the inhibitory effect of the troponin-tropomyosin complex on actin-myosin interaction. Which biophysical consequence will be most associated with this post-translational modification?
A research team discovers a novel post-translational modification on troponin I (TnI) that selectively alters its interaction with tropomyosin. This modification, termed 'Phospho-Inhibition,' occurs specifically at a serine residue located near the C-terminus of TnI and enhances the inhibitory effect of the troponin-tropomyosin complex on actin-myosin interaction. Which biophysical consequence will be most associated with this post-translational modification?
Researchers are comparing the structural organization of skeletal muscle sarcomeres in two different species of mammals: Species A, which is known for its exceptional jumping ability, and Species B, which is adapted for sustained endurance running. They observe that the sarcomeres in Species A exhibit a significantly higher proportion of short, thick filaments and a lower proportion of long, thin filaments compared to Species B. What functional advantage does this provide Species A?
Researchers are comparing the structural organization of skeletal muscle sarcomeres in two different species of mammals: Species A, which is known for its exceptional jumping ability, and Species B, which is adapted for sustained endurance running. They observe that the sarcomeres in Species A exhibit a significantly higher proportion of short, thick filaments and a lower proportion of long, thin filaments compared to Species B. What functional advantage does this provide Species A?
A research group is investigating the role of the extracellular matrix (ECM) in regulating skeletal muscle fiber size and function. They discover that a specific ECM protein, 'FibroModulin-X,' is essential for maintaining the structural integrity of the muscle fiber basal lamina. Deletion of 'FibroModulin-X' in mice leads to a progressive disruption of the basal lamina, resulting in muscle fiber atrophy and impaired force transmission. What mechanism would be most associated with direct regulation of muscle fiber size?
A research group is investigating the role of the extracellular matrix (ECM) in regulating skeletal muscle fiber size and function. They discover that a specific ECM protein, 'FibroModulin-X,' is essential for maintaining the structural integrity of the muscle fiber basal lamina. Deletion of 'FibroModulin-X' in mice leads to a progressive disruption of the basal lamina, resulting in muscle fiber atrophy and impaired force transmission. What mechanism would be most associated with direct regulation of muscle fiber size?
A researcher is studying the effects of aging on skeletal muscle function and observes a significant decline in the number of satellite cells in the muscles of elderly individuals. Furthermore, they find that the remaining satellite cells exhibit reduced proliferative capacity and impaired differentiation potential. Which is the most associated functional consequence resulting from this satellite cell dysfunction?
A researcher is studying the effects of aging on skeletal muscle function and observes a significant decline in the number of satellite cells in the muscles of elderly individuals. Furthermore, they find that the remaining satellite cells exhibit reduced proliferative capacity and impaired differentiation potential. Which is the most associated functional consequence resulting from this satellite cell dysfunction?
A researcher is investigating the effects of a novel compound on skeletal muscle contraction. They observe that the compound significantly increases the rate of ATP hydrolysis by myosin ATPase, but simultaneously reduces the affinity of myosin for actin. Considering these opposing effects, which of the following outcomes would most likely be observed regarding muscle force production?
A researcher is investigating the effects of a novel compound on skeletal muscle contraction. They observe that the compound significantly increases the rate of ATP hydrolysis by myosin ATPase, but simultaneously reduces the affinity of myosin for actin. Considering these opposing effects, which of the following outcomes would most likely be observed regarding muscle force production?
In a study of skeletal muscle adaptation to exercise, researchers discover that a specific microRNA, 'miR-499,' is upregulated in response to resistance training. 'miR-499' directly targets and inhibits the expression of a protein, 'MyoInhibin,' which normally suppresses the activity of the mammalian target of rapamycin (mTOR) signaling pathway. Based on these findings, what is the most likely outcome of 'miR-499' upregulation in resistance-trained muscle?
In a study of skeletal muscle adaptation to exercise, researchers discover that a specific microRNA, 'miR-499,' is upregulated in response to resistance training. 'miR-499' directly targets and inhibits the expression of a protein, 'MyoInhibin,' which normally suppresses the activity of the mammalian target of rapamycin (mTOR) signaling pathway. Based on these findings, what is the most likely outcome of 'miR-499' upregulation in resistance-trained muscle?
Consider a scenario where a genetic mutation leads to a complete loss of function of the nebulin protein in skeletal muscle fibers. How would this mutation most directly impact muscle structure and function?
Consider a scenario where a genetic mutation leads to a complete loss of function of the nebulin protein in skeletal muscle fibers. How would this mutation most directly impact muscle structure and function?
A team of scientists is investigating the effects of a novel drug, 'MyoRestore,' on aged skeletal muscle. They find that 'MyoRestore' selectively enhances the fusion of satellite cells with existing muscle fibers and promotes the formation of new myofibers. Which cellular and molecular mechanisms would most likely be involved in mediating the beneficial effects of 'MyoRestore'?
A team of scientists is investigating the effects of a novel drug, 'MyoRestore,' on aged skeletal muscle. They find that 'MyoRestore' selectively enhances the fusion of satellite cells with existing muscle fibers and promotes the formation of new myofibers. Which cellular and molecular mechanisms would most likely be involved in mediating the beneficial effects of 'MyoRestore'?
Researchers are studying the effects of a chronic inflammatory condition on skeletal muscle metabolism. They observe a significant increase in the expression of myostatin, a negative regulator of muscle growth, and a corresponding decrease in the activity of insulin-like growth factor 1 (IGF-1) signaling pathway. Given these changes, how would this condition affect glucose uptake?
Researchers are studying the effects of a chronic inflammatory condition on skeletal muscle metabolism. They observe a significant increase in the expression of myostatin, a negative regulator of muscle growth, and a corresponding decrease in the activity of insulin-like growth factor 1 (IGF-1) signaling pathway. Given these changes, how would this condition affect glucose uptake?
Consider a scenario where a patient is diagnosed with a rare genetic disorder characterized by a mutation in the gene encoding for the dihydropyridine receptor (DHPR) in skeletal muscle cells. This mutation impairs the ability of DHPR to undergo conformational changes in response to sarcolemma depolarization. What downstream effect will this mutation have?
Consider a scenario where a patient is diagnosed with a rare genetic disorder characterized by a mutation in the gene encoding for the dihydropyridine receptor (DHPR) in skeletal muscle cells. This mutation impairs the ability of DHPR to undergo conformational changes in response to sarcolemma depolarization. What downstream effect will this mutation have?
A researcher is investigating the effects of a novel compound, 'MyoBlock,' on skeletal muscle contraction. They discover that 'MyoBlock' selectively inhibits the interaction between troponin and tropomyosin in skeletal muscle cells. Which alteration will most likely be observed?
A researcher is investigating the effects of a novel compound, 'MyoBlock,' on skeletal muscle contraction. They discover that 'MyoBlock' selectively inhibits the interaction between troponin and tropomyosin in skeletal muscle cells. Which alteration will most likely be observed?
In a study, researchers examine the effects of prolonged immobilization on skeletal muscle properties. They observe a significant decrease in the angle of pennation of muscle fibers within the immobilized muscle. What is the most likely explanation?
In a study, researchers examine the effects of prolonged immobilization on skeletal muscle properties. They observe a significant decrease in the angle of pennation of muscle fibers within the immobilized muscle. What is the most likely explanation?
Researchers are investigating the mechanisms underlying muscle fatigue during high-intensity exercise. They observe a significant accumulation of inorganic phosphate (Pi) within skeletal muscle cells. Which mechanisms primarily account for the role of Pi in muscle fatigue?
Researchers are investigating the mechanisms underlying muscle fatigue during high-intensity exercise. They observe a significant accumulation of inorganic phosphate (Pi) within skeletal muscle cells. Which mechanisms primarily account for the role of Pi in muscle fatigue?
A research team is studying the effects of a novel genetic mutation on the length-tension relationship in skeletal muscle fibers. They observe that muscle fibers expressing the mutant gene exhibit a significantly reduced optimal length for force production. Which structural and functional alterations would occur?
A research team is studying the effects of a novel genetic mutation on the length-tension relationship in skeletal muscle fibers. They observe that muscle fibers expressing the mutant gene exhibit a significantly reduced optimal length for force production. Which structural and functional alterations would occur?
In a study comparing skeletal muscle function between sedentary individuals and elite endurance athletes, researchers observe significant differences in the expression of specific metabolic enzymes. Which metabolic adaptation would most likely be observed?
In a study comparing skeletal muscle function between sedentary individuals and elite endurance athletes, researchers observe significant differences in the expression of specific metabolic enzymes. Which metabolic adaptation would most likely be observed?
Consider someone who has McArdle's disease, where there is a deficiency in muscle glycogen phosphorylase. How is their muscle function most directly affected?
Consider someone who has McArdle's disease, where there is a deficiency in muscle glycogen phosphorylase. How is their muscle function most directly affected?
A patient is diagnosed with malignant hyperthermia during surgery. This condition is characterized by uncontrolled calcium release from the sarcoplasmic reticulum in skeletal muscle cells, leading to sustained muscle contraction, hyperthermia, and metabolic crisis. What drug will most effectively counteract the conditions?
A patient is diagnosed with malignant hyperthermia during surgery. This condition is characterized by uncontrolled calcium release from the sarcoplasmic reticulum in skeletal muscle cells, leading to sustained muscle contraction, hyperthermia, and metabolic crisis. What drug will most effectively counteract the conditions?
During a physiological study, researchers isolate a skeletal muscle fiber and observe that it has a significantly higher proportion of myosin heavy chain (MHC) IIx isoforms compared to MHC I isoforms. Which traits will most likely be seen in this muscle fiber?
During a physiological study, researchers isolate a skeletal muscle fiber and observe that it has a significantly higher proportion of myosin heavy chain (MHC) IIx isoforms compared to MHC I isoforms. Which traits will most likely be seen in this muscle fiber?
A scientist is studying the impact of a novel toxin on skeletal muscle function. They discover that the toxin selectively disrupts the function of the sarcolemma's voltage-gated sodium channels. How will this disrupt muscle contraction?
A scientist is studying the impact of a novel toxin on skeletal muscle function. They discover that the toxin selectively disrupts the function of the sarcolemma's voltage-gated sodium channels. How will this disrupt muscle contraction?
Consider a novel therapeutic strategy involving targeted disruption of desmin protein organization at the M-line within skeletal muscle sarcomeres. Which functional consequence is most likely to arise from this intervention, assuming no compensatory mechanisms are activated?
Consider a novel therapeutic strategy involving targeted disruption of desmin protein organization at the M-line within skeletal muscle sarcomeres. Which functional consequence is most likely to arise from this intervention, assuming no compensatory mechanisms are activated?
Imagine a hypothetical scenario where a novel, highly potent acetylcholinesterase (AChE) inhibitor, 'Hypercholine,' is introduced into the synaptic cleft of a neuromuscular junction. Assuming that 'Hypercholine' completely abolishes AChE activity, which of the following outcomes would likely ensue?
Imagine a hypothetical scenario where a novel, highly potent acetylcholinesterase (AChE) inhibitor, 'Hypercholine,' is introduced into the synaptic cleft of a neuromuscular junction. Assuming that 'Hypercholine' completely abolishes AChE activity, which of the following outcomes would likely ensue?
A research team discovers a novel protein, 'SarcoGuard,' that specifically interacts with the voltage-gated sodium channels in the sarcolemma of skeletal muscle fibers. 'SarcoGuard' enhances the rate of sodium channel inactivation following membrane depolarization. What is the most expected consequence?
A research team discovers a novel protein, 'SarcoGuard,' that specifically interacts with the voltage-gated sodium channels in the sarcolemma of skeletal muscle fibers. 'SarcoGuard' enhances the rate of sodium channel inactivation following membrane depolarization. What is the most expected consequence?
A novel compound, 'MyoCalibrator,' is designed to specifically modulate the calcium sensitivity of skeletal muscle fibers without affecting maximal calcium-activated force. 'MyoCalibrator' allosterically modifies the troponin complex, enhancing its affinity for calcium ions. What is the most anticipated outcome?
A novel compound, 'MyoCalibrator,' is designed to specifically modulate the calcium sensitivity of skeletal muscle fibers without affecting maximal calcium-activated force. 'MyoCalibrator' allosterically modifies the troponin complex, enhancing its affinity for calcium ions. What is the most anticipated outcome?
Consider a mutation that impairs the ability of the dihydropyridine receptor (DHPR) to interact physically with the ryanodine receptor (RyR1) in skeletal muscle cells, but does not affect the voltage-sensing properties of DHPR. How is excitation-contraction coupling affected?
Consider a mutation that impairs the ability of the dihydropyridine receptor (DHPR) to interact physically with the ryanodine receptor (RyR1) in skeletal muscle cells, but does not affect the voltage-sensing properties of DHPR. How is excitation-contraction coupling affected?
Researchers discover a novel post-translational modification on myosin light chain kinase (MLCK) that prevents its activation by calcium-calmodulin. They introduce this modified MLCK into smooth muscle cells. What is the most likely outcome?
Researchers discover a novel post-translational modification on myosin light chain kinase (MLCK) that prevents its activation by calcium-calmodulin. They introduce this modified MLCK into smooth muscle cells. What is the most likely outcome?
Imagine a scenario where a novel toxin, 'FibroDisruptor,' selectively degrades collagen type IV within the basal lamina of skeletal muscle fibers. Which resulting structural and functional alteration would most likely occur?
Imagine a scenario where a novel toxin, 'FibroDisruptor,' selectively degrades collagen type IV within the basal lamina of skeletal muscle fibers. Which resulting structural and functional alteration would most likely occur?
A research group is investigating the effects of chronic exposure to a novel myotoxin, 'Atrophycin-X,' on skeletal muscle fibers. They observe a significant down-regulation of the ubiquitin-proteasome system (UPS) in treated muscle cells. Which process is mostly to occur?
A research group is investigating the effects of chronic exposure to a novel myotoxin, 'Atrophycin-X,' on skeletal muscle fibers. They observe a significant down-regulation of the ubiquitin-proteasome system (UPS) in treated muscle cells. Which process is mostly to occur?
In a groundbreaking study, researchers have identified a novel microRNA, 'miR-X,' that is specifically expressed in slow-twitch (type I) skeletal muscle fibers. 'miR-X' directly targets and inhibits the expression of a key enzyme involved in glycogenolysis. What would be the most likely consequence?
In a groundbreaking study, researchers have identified a novel microRNA, 'miR-X,' that is specifically expressed in slow-twitch (type I) skeletal muscle fibers. 'miR-X' directly targets and inhibits the expression of a key enzyme involved in glycogenolysis. What would be the most likely consequence?
A researcher discovers a novel mutation in the titin protein that specifically affects its interaction with the Z-disc. The mutant titin protein is still able to span the length of the sarcomere and interact with actin and myosin, but its binding affinity for proteins at the Z-disc is significantly reduced. What structural/functional alterations occur?
A researcher discovers a novel mutation in the titin protein that specifically affects its interaction with the Z-disc. The mutant titin protein is still able to span the length of the sarcomere and interact with actin and myosin, but its binding affinity for proteins at the Z-disc is significantly reduced. What structural/functional alterations occur?
A patient is diagnosed with a rare genetic disorder characterized by a complete absence of the protein myogenin in skeletal muscle tissue. Which is the most likely outcome?
A patient is diagnosed with a rare genetic disorder characterized by a complete absence of the protein myogenin in skeletal muscle tissue. Which is the most likely outcome?
Consider a scenario where a researcher introduces a non-hydrolyzable analog of GTP into skeletal muscle cells, specifically targeting the Gαq subunit of G proteins coupled to phospholipase C (PLC). How would be contraction affected?
Consider a scenario where a researcher introduces a non-hydrolyzable analog of GTP into skeletal muscle cells, specifically targeting the Gαq subunit of G proteins coupled to phospholipase C (PLC). How would be contraction affected?
Researchers isolate a novel compound, 'Desminex,' that selectively inhibits the polymerization of desmin intermediate filaments in skeletal muscle cells. How would the compound impact the structural integrity?
Researchers isolate a novel compound, 'Desminex,' that selectively inhibits the polymerization of desmin intermediate filaments in skeletal muscle cells. How would the compound impact the structural integrity?
A research team discovers a novel epigenetic modification that selectively silences the gene encoding for the muscle-specific microRNA, miR-133, in skeletal muscle cells. What is the most anticipated effect?
A research team discovers a novel epigenetic modification that selectively silences the gene encoding for the muscle-specific microRNA, miR-133, in skeletal muscle cells. What is the most anticipated effect?
Researchers are studying the effects of long-term spaceflight on skeletal muscle function. They observe a significant increase in the expression of the E3 ubiquitin ligase MuRF1 in the muscles of astronauts. What process will the muscle cells exhibit?
Researchers are studying the effects of long-term spaceflight on skeletal muscle function. They observe a significant increase in the expression of the E3 ubiquitin ligase MuRF1 in the muscles of astronauts. What process will the muscle cells exhibit?
Suppose you want to test the impact of downregulating the expression of calsequestrin in the sarcoplasmic reticulum (SR) of skeletal muscle fibers. What is the most likely effect on intracellular calcium transients during muscle stimulation?
Suppose you want to test the impact of downregulating the expression of calsequestrin in the sarcoplasmic reticulum (SR) of skeletal muscle fibers. What is the most likely effect on intracellular calcium transients during muscle stimulation?
In a study of muscle adaptation to extreme endurance exercise, researchers discover a novel long non-coding RNA (lncRNA) that is highly upregulated in the skeletal muscles of elite marathon runners. This lncRNA, termed 'Enduro-lnc,' interacts with and stabilizes mRNA of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). What will be the metabolic and structural impact?
In a study of muscle adaptation to extreme endurance exercise, researchers discover a novel long non-coding RNA (lncRNA) that is highly upregulated in the skeletal muscles of elite marathon runners. This lncRNA, termed 'Enduro-lnc,' interacts with and stabilizes mRNA of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). What will be the metabolic and structural impact?
A researcher is investigating the effects of a novel compound, 'MyoAgeReverse,' on senescent skeletal muscle cells in vitro. They observe that 'MyoAgeReverse' specifically inhibits the activity of the DNA methyltransferase enzyme DNMT1! What is the result?
A researcher is investigating the effects of a novel compound, 'MyoAgeReverse,' on senescent skeletal muscle cells in vitro. They observe that 'MyoAgeReverse' specifically inhibits the activity of the DNA methyltransferase enzyme DNMT1! What is the result?
Consider a scenario where a mutation leads to a complete loss of function of the obscurin protein in skeletal muscle fibers. What is the most direct impact on muscle structure and function?
Consider a scenario where a mutation leads to a complete loss of function of the obscurin protein in skeletal muscle fibers. What is the most direct impact on muscle structure and function?
Researchers are investigating the effects of a novel drug, 'MyoRegenX,' on skeletal muscle regeneration following injury. They find that 'MyoRegenX' selectively enhances the expression of the transcription factor Pax7 in satellite cells. What is the expected result?
Researchers are investigating the effects of a novel drug, 'MyoRegenX,' on skeletal muscle regeneration following injury. They find that 'MyoRegenX' selectively enhances the expression of the transcription factor Pax7 in satellite cells. What is the expected result?
Consider a scenario where a chronic inflammatory condition leads to sustained activation of the transcription factor NF-κB in skeletal muscle cells. How will activation affect glucose uptake and metabolism?
Consider a scenario where a chronic inflammatory condition leads to sustained activation of the transcription factor NF-κB in skeletal muscle cells. How will activation affect glucose uptake and metabolism?
Researchers discover that a mutation in the gene encoding for the sarcoplasmic reticulum calcium ATPase (SERCA) pump results in a significantly reduced affinity of the pump for calcium ions. How is the pump altered?
Researchers discover that a mutation in the gene encoding for the sarcoplasmic reticulum calcium ATPase (SERCA) pump results in a significantly reduced affinity of the pump for calcium ions. How is the pump altered?
Researchers are investigating the effects of a novel compound, 'MyoStasis,' on skeletal muscle homeostasis. They find that 'MyoStasis' selectively inhibits the activity of the FOXO transcription factors in skeletal muscle cells. Which processes is most likely to be affected?
Researchers are investigating the effects of a novel compound, 'MyoStasis,' on skeletal muscle homeostasis. They find that 'MyoStasis' selectively inhibits the activity of the FOXO transcription factors in skeletal muscle cells. Which processes is most likely to be affected?
A study examines the effects of prolonged immobilization on skeletal muscle properties. They observe a significant increase in the proportion of hybrid muscle fibers expressing both slow and fast myosin heavy chain isoforms. What would this increase indicate?
A study examines the effects of prolonged immobilization on skeletal muscle properties. They observe a significant increase in the proportion of hybrid muscle fibers expressing both slow and fast myosin heavy chain isoforms. What would this increase indicate?
Researchers are investigating the mechanisms underlying muscle fatigue during high-intensity exercise. They observe a significant decrease in pH within skeletal muscle cells. How does this affect muscle contraction?
Researchers are investigating the mechanisms underlying muscle fatigue during high-intensity exercise. They observe a significant decrease in pH within skeletal muscle cells. How does this affect muscle contraction?
Which structural and functional alterations would likely occur in muscle fibers expressing a mutant form of the giant protein nebulin that is unable to bind to actin filaments?
Which structural and functional alterations would likely occur in muscle fibers expressing a mutant form of the giant protein nebulin that is unable to bind to actin filaments?
In a study comparing skeletal muscle function between sedentary individuals and elite powerlifters, researchers observe significant differences in the expression of specific ion channels. Which change would be observed?
In a study comparing skeletal muscle function between sedentary individuals and elite powerlifters, researchers observe significant differences in the expression of specific ion channels. Which change would be observed?
Consider a patient with a mutation affecting the function of the ryanodine receptor (RyR1) channel in skeletal muscle. This leads to excessive calcium permeability. How is their muscle function mostly affected?
Consider a patient with a mutation affecting the function of the ryanodine receptor (RyR1) channel in skeletal muscle. This leads to excessive calcium permeability. How is their muscle function mostly affected?
A patient is diagnosed with a rare form of congenital myopathy characterized by a mutation in the gene encoding for myostatin, resulting in a complete loss of myostatin protein expression in skeletal muscle. What outcome is most likely?
A patient is diagnosed with a rare form of congenital myopathy characterized by a mutation in the gene encoding for myostatin, resulting in a complete loss of myostatin protein expression in skeletal muscle. What outcome is most likely?
Scientists want to use a novel toxin that selectively disrupts the function of the T-tubules in skeletal muscle fibers, while leaving the sarcolemma intact. How will this cause dysfunction?
Scientists want to use a novel toxin that selectively disrupts the function of the T-tubules in skeletal muscle fibers, while leaving the sarcolemma intact. How will this cause dysfunction?
Imagine a scenario in which a mutation in skeletal muscle cells results in a myosin heavy chain isoform with a significantly reduced duty cycle (the fraction of time myosin is strongly bound to actin during each ATP hydrolysis cycle). How would this change the muscle fiber?
Imagine a scenario in which a mutation in skeletal muscle cells results in a myosin heavy chain isoform with a significantly reduced duty cycle (the fraction of time myosin is strongly bound to actin during each ATP hydrolysis cycle). How would this change the muscle fiber?
A research team discovers a novel molecule, 'MyoAtrophyBlock,' that selectively inhibits the activity of the enzyme cathepsin L in skeletal muscle cells! What will happen?
A research team discovers a novel molecule, 'MyoAtrophyBlock,' that selectively inhibits the activity of the enzyme cathepsin L in skeletal muscle cells! What will happen?
Consider a scenario where a patient is diagnosed with a rare genetic disorder characterized by a mutation in the gene encoding for glycogen synthase in skeletal muscle cells. This mutation results in a complete loss of glycogen synthase activity. How is their metabolism affected?
Consider a scenario where a patient is diagnosed with a rare genetic disorder characterized by a mutation in the gene encoding for glycogen synthase in skeletal muscle cells. This mutation results in a complete loss of glycogen synthase activity. How is their metabolism affected?
In a hypothetical scenario, a researcher discovers a novel mutation in the gene encoding the voltage-gated sodium channel Nav1.4, specifically expressed in skeletal muscle. This mutation results in a channel with a significantly reduced rate of inactivation, causing prolonged sodium influx during depolarization. Assuming all other ion channel kinetics and conductances remain unchanged, how would this mutation primarily affect the repolarization phase of the sarcolemma action potential in skeletal muscle fibers?
In a hypothetical scenario, a researcher discovers a novel mutation in the gene encoding the voltage-gated sodium channel Nav1.4, specifically expressed in skeletal muscle. This mutation results in a channel with a significantly reduced rate of inactivation, causing prolonged sodium influx during depolarization. Assuming all other ion channel kinetics and conductances remain unchanged, how would this mutation primarily affect the repolarization phase of the sarcolemma action potential in skeletal muscle fibers?
Consider a scenario where a researcher is investigating the effects of a novel compound, 'Repolarin,' on skeletal muscle excitability. In isolated muscle fibers, they observe that 'Repolarin' selectively enhances the activity of voltage-gated potassium channels, leading to a substantial increase in potassium efflux during the repolarization phase of the action potential. Intracellular recordings reveal a significantly shortened action potential duration and a more negative resting membrane potential. Which of the subsequent changes would most likely be observed in the electrical properties of skeletal muscle fibers treated with 'Repolarin'?
Consider a scenario where a researcher is investigating the effects of a novel compound, 'Repolarin,' on skeletal muscle excitability. In isolated muscle fibers, they observe that 'Repolarin' selectively enhances the activity of voltage-gated potassium channels, leading to a substantial increase in potassium efflux during the repolarization phase of the action potential. Intracellular recordings reveal a significantly shortened action potential duration and a more negative resting membrane potential. Which of the subsequent changes would most likely be observed in the electrical properties of skeletal muscle fibers treated with 'Repolarin'?
A research team is investigating the effects of a novel mutation in the gene encoding for acetylcholinesterase (AChE) at the neuromuscular junction. This mutation results in an AChE enzyme with a significantly reduced catalytic activity. In a series of experiments, they observe that the half-life of acetylcholine (ACh) in the synaptic cleft is markedly prolonged. Which of the following downstream consequences would most likely be observed at the neuromuscular junction of individuals carrying this mutation?
A research team is investigating the effects of a novel mutation in the gene encoding for acetylcholinesterase (AChE) at the neuromuscular junction. This mutation results in an AChE enzyme with a significantly reduced catalytic activity. In a series of experiments, they observe that the half-life of acetylcholine (ACh) in the synaptic cleft is markedly prolonged. Which of the following downstream consequences would most likely be observed at the neuromuscular junction of individuals carrying this mutation?
Consider a scenario where a novel synthetic peptide, 'CurareMimic-X,' is designed to specifically disrupt the function of the nicotinic acetylcholine receptor (nAChR) at the neuromuscular junction. Unlike curare, which competitively binds to the ACh binding site, 'CurareMimic-X' allosterically modulates the nAChR, inducing a conformational change that prevents channel opening, even after ACh binding. Electrophysiological studies reveal that 'CurareMimic-X' significantly reduces the frequency of channel opening events without altering the single-channel conductance. Which of the following effects would most likely result from the application of 'CurareMimic-X' at the neuromuscular junction?
Consider a scenario where a novel synthetic peptide, 'CurareMimic-X,' is designed to specifically disrupt the function of the nicotinic acetylcholine receptor (nAChR) at the neuromuscular junction. Unlike curare, which competitively binds to the ACh binding site, 'CurareMimic-X' allosterically modulates the nAChR, inducing a conformational change that prevents channel opening, even after ACh binding. Electrophysiological studies reveal that 'CurareMimic-X' significantly reduces the frequency of channel opening events without altering the single-channel conductance. Which of the following effects would most likely result from the application of 'CurareMimic-X' at the neuromuscular junction?
Researchers discover a novel protein, 'SynaptoBreaker,' which selectively cleaves the SNARE protein synaptobrevin-2 specifically at inhibitory neuromuscular junctions. Which of the following consequences would most likely result from the action of 'SynaptoBreaker'?
Researchers discover a novel protein, 'SynaptoBreaker,' which selectively cleaves the SNARE protein synaptobrevin-2 specifically at inhibitory neuromuscular junctions. Which of the following consequences would most likely result from the action of 'SynaptoBreaker'?
Consider a transgenic mouse model engineered to express a constitutively active form of Rho-associated protein kinase (ROCK) specifically in skeletal muscle cells. ROCK is a serine/threonine kinase known to regulate various cellular processes, including cytoskeletal dynamics and contractility, primarily through phosphorylation of myosin light chain phosphatase (MLCP), thereby inhibiting its activity. How would a researcher observe that activation of ROCK affects muscle?
Consider a transgenic mouse model engineered to express a constitutively active form of Rho-associated protein kinase (ROCK) specifically in skeletal muscle cells. ROCK is a serine/threonine kinase known to regulate various cellular processes, including cytoskeletal dynamics and contractility, primarily through phosphorylation of myosin light chain phosphatase (MLCP), thereby inhibiting its activity. How would a researcher observe that activation of ROCK affects muscle?
A researcher is studying the force-velocity relationship in isolated skeletal muscle fibers from two different mouse strains: Wild-type (WT) and Mutant (MT). They observe that, at any given submaximal load, MT fibers exhibit a significantly lower shortening velocity compared to WT fibers. Further analysis reveals no significant differences in myosin ATPase activity or calcium sensitivity between the two strains. However, electron microscopy reveals a marked increase in the number of non-contractile, viscoelastic elements (e.g., intermediate filaments, extracellular matrix proteins) within the MT fibers. How would we primarily describe the effect of increased non-contractile components?
A researcher is studying the force-velocity relationship in isolated skeletal muscle fibers from two different mouse strains: Wild-type (WT) and Mutant (MT). They observe that, at any given submaximal load, MT fibers exhibit a significantly lower shortening velocity compared to WT fibers. Further analysis reveals no significant differences in myosin ATPase activity or calcium sensitivity between the two strains. However, electron microscopy reveals a marked increase in the number of non-contractile, viscoelastic elements (e.g., intermediate filaments, extracellular matrix proteins) within the MT fibers. How would we primarily describe the effect of increased non-contractile components?
Consider a novel therapeutic intervention designed to selectively enhance the expression and activity of the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump in skeletal muscle fibers of patients with severe muscle atrophy. This therapy aims to improve calcium handling and excitation-contraction coupling efficiency. Assuming all other factors remain constant, which of the following outcomes would be most likely regarding muscle force?
Consider a novel therapeutic intervention designed to selectively enhance the expression and activity of the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump in skeletal muscle fibers of patients with severe muscle atrophy. This therapy aims to improve calcium handling and excitation-contraction coupling efficiency. Assuming all other factors remain constant, which of the following outcomes would be most likely regarding muscle force?
A researcher is studying the effects of a novel mutation in the gene encoding for troponin C (TnC) in skeletal muscle fibers. The mutation results in a TnC protein with a significantly reduced affinity for calcium ions. In isolated muscle fiber experiments, they observe that the force-pCa relationship is right-shifted, indicating a lower calcium sensitivity. What is the most likely downstream effect?
A researcher is studying the effects of a novel mutation in the gene encoding for troponin C (TnC) in skeletal muscle fibers. The mutation results in a TnC protein with a significantly reduced affinity for calcium ions. In isolated muscle fiber experiments, they observe that the force-pCa relationship is right-shifted, indicating a lower calcium sensitivity. What is the most likely downstream effect?
Consider a scenario where a novel myotoxin, 'Sarcomerase,' is engineered to selectively cleave the Z-discs in skeletal muscle sarcomeres. The cleavage occurs in a manner that disrupts the structural integrity of the Z-discs without directly affecting the actin or myosin filaments. Which downstream alteration would be associated?
Consider a scenario where a novel myotoxin, 'Sarcomerase,' is engineered to selectively cleave the Z-discs in skeletal muscle sarcomeres. The cleavage occurs in a manner that disrupts the structural integrity of the Z-discs without directly affecting the actin or myosin filaments. Which downstream alteration would be associated?
A research team discovers a novel compound, 'MyoD-Activator,' that selectively enhances the expression and activity of the myogenic regulatory factor MyoD in skeletal muscle satellite cells. In a mouse model of Duchenne muscular dystrophy (DMD), they administer 'MyoD-Activator' and observe a significant improvement in muscle regeneration and function. Which mechanism is most likely mediating the therapeutic effect?
A research team discovers a novel compound, 'MyoD-Activator,' that selectively enhances the expression and activity of the myogenic regulatory factor MyoD in skeletal muscle satellite cells. In a mouse model of Duchenne muscular dystrophy (DMD), they administer 'MyoD-Activator' and observe a significant improvement in muscle regeneration and function. Which mechanism is most likely mediating the therapeutic effect?
Consider a population of skeletal muscle fibers in which a novel mutation leads to a constitutive activation of glycogen synthase kinase-3β (GSK-3β). Furthermore, these muscle fibers also show a marked decrease in the expression of heat shock proteins (HSPs). How would this change metabolism?
Consider a population of skeletal muscle fibers in which a novel mutation leads to a constitutive activation of glycogen synthase kinase-3β (GSK-3β). Furthermore, these muscle fibers also show a marked decrease in the expression of heat shock proteins (HSPs). How would this change metabolism?
A team of bioengineers constructs an artificial neuromuscular junction (NMJ) using microfluidic technology. The artificial NMJ consists of a motor neuron-like cell and a skeletal muscle fiber-like cell, separated by a microchannel representing the synaptic cleft. They introduce a modified form of botulinum toxin serotype A (BoNT/A) that selectively cleaves syntaxin-1 at the artificial NMJ. What will happen?
A team of bioengineers constructs an artificial neuromuscular junction (NMJ) using microfluidic technology. The artificial NMJ consists of a motor neuron-like cell and a skeletal muscle fiber-like cell, separated by a microchannel representing the synaptic cleft. They introduce a modified form of botulinum toxin serotype A (BoNT/A) that selectively cleaves syntaxin-1 at the artificial NMJ. What will happen?
In a scenario where a novel mutation in the gene encoding for muscle LIM protein (MLP) results in a complete loss of MLP function in skeletal muscle cells, which alteration would be most likely?
In a scenario where a novel mutation in the gene encoding for muscle LIM protein (MLP) results in a complete loss of MLP function in skeletal muscle cells, which alteration would be most likely?
Consider a novel gene therapy approach designed to selectively overexpress the small heat shock protein (sHSP) HspB1 in skeletal muscle fibers. The hypothesis is that HspB1 overexpression will enhance muscle resistance to stress and improve overall function. What should happen?
Consider a novel gene therapy approach designed to selectively overexpress the small heat shock protein (sHSP) HspB1 in skeletal muscle fibers. The hypothesis is that HspB1 overexpression will enhance muscle resistance to stress and improve overall function. What should happen?
Researchers are investigating the effects of a novel compound, 'MyoTweak,' on skeletal muscle fiber type composition. They observe that 'MyoTweak' selectively promotes the expression of slow-twitch (Type I) myosin heavy chain (MHC) isoforms while simultaneously suppressing the expression of fast-twitch (Type II) MHC isoforms, what outcome is most likely?
Researchers are investigating the effects of a novel compound, 'MyoTweak,' on skeletal muscle fiber type composition. They observe that 'MyoTweak' selectively promotes the expression of slow-twitch (Type I) myosin heavy chain (MHC) isoforms while simultaneously suppressing the expression of fast-twitch (Type II) MHC isoforms, what outcome is most likely?
A scientist creates a scenario. A mutation in the gene encoding for the ryanodine receptor (RyR1) in skeletal muscle cells results in a channel with a significantly increased sensitivity to calcium ions. This means that lower concentrations of calcium are required to activate RyR1 and trigger calcium release from the sarcoplasmic reticulum. What will happen?
A scientist creates a scenario. A mutation in the gene encoding for the ryanodine receptor (RyR1) in skeletal muscle cells results in a channel with a significantly increased sensitivity to calcium ions. This means that lower concentrations of calcium are required to activate RyR1 and trigger calcium release from the sarcoplasmic reticulum. What will happen?
A team of researchers is investigating the effects of a novel microRNA, 'miR-MuscleGuard,' on skeletal muscle aging. They observe that 'miR-MuscleGuard' expression is significantly reduced in aged muscle tissue, and that restoring its expression improves muscle function in old mice. Further investigation reveals that 'miR-MuscleGuard' directly targets and inhibits the expression of a gene encoding for a protein involved in cellular senescence. Thus, what happens if miR-MuscleGuard works?
A team of researchers is investigating the effects of a novel microRNA, 'miR-MuscleGuard,' on skeletal muscle aging. They observe that 'miR-MuscleGuard' expression is significantly reduced in aged muscle tissue, and that restoring its expression improves muscle function in old mice. Further investigation reveals that 'miR-MuscleGuard' directly targets and inhibits the expression of a gene encoding for a protein involved in cellular senescence. Thus, what happens if miR-MuscleGuard works?
Consider a hypothetical toxin that selectively disrupts the function of the dystroglycan complex in skeletal muscle fibers. Focus on the connection provided with the extracellular matrix. What occurs?
Consider a hypothetical toxin that selectively disrupts the function of the dystroglycan complex in skeletal muscle fibers. Focus on the connection provided with the extracellular matrix. What occurs?
A researcher discovers a novel post-translational modification on titin that selectively alters its interaction with the M-line proteins within the sarcomere. This modification, termed 'M-Inhibitor,' reduces the binding affinity between titin and M-line components, without affecting its interaction with the Z-disc. Muscle will likely experience:
A researcher discovers a novel post-translational modification on titin that selectively alters its interaction with the M-line proteins within the sarcomere. This modification, termed 'M-Inhibitor,' reduces the binding affinity between titin and M-line components, without affecting its interaction with the Z-disc. Muscle will likely experience:
Consider a scenario involving a conditional knockout mouse model in which the gene encoding for the muscle-specific microRNA, miR-1, is selectively deleted in skeletal muscle cells during adulthood. What is the impact to the animal?
Consider a scenario involving a conditional knockout mouse model in which the gene encoding for the muscle-specific microRNA, miR-1, is selectively deleted in skeletal muscle cells during adulthood. What is the impact to the animal?
A research team identifies a mutation in the gene encoding for the transcription factor myogenin, specifically affecting its DNA-binding domain. While the mutant myogenin protein is still expressed at normal levels, it is unable to bind to its target DNA sequences. How will the mutant myogenin affect muscle cells?
A research team identifies a mutation in the gene encoding for the transcription factor myogenin, specifically affecting its DNA-binding domain. While the mutant myogenin protein is still expressed at normal levels, it is unable to bind to its target DNA sequences. How will the mutant myogenin affect muscle cells?
Researchers discover a novel compound, 'MyoSynapse,' that selectively enhances the formation and maintenance of neuromuscular junctions (NMJs) in skeletal muscle. This compound promotes the clustering of acetylcholine receptors (AChRs) at the postsynaptic membrane and increases the branching of motor neuron terminals. What will this look like?
Researchers discover a novel compound, 'MyoSynapse,' that selectively enhances the formation and maintenance of neuromuscular junctions (NMJs) in skeletal muscle. This compound promotes the clustering of acetylcholine receptors (AChRs) at the postsynaptic membrane and increases the branching of motor neuron terminals. What will this look like?
A scenario where a novel mutation in the gene encoding for the enzyme glycogen phosphorylase kinase (PhK) results in a complete loss of PhK activity in skeletal muscle. Glycogen phosphorylase kinase is essential for activating glycogen phosphorylase, the enzyme responsible for breaking down glycogen into glucose-1-phosphate. How will this affect the muscle?
A scenario where a novel mutation in the gene encoding for the enzyme glycogen phosphorylase kinase (PhK) results in a complete loss of PhK activity in skeletal muscle. Glycogen phosphorylase kinase is essential for activating glycogen phosphorylase, the enzyme responsible for breaking down glycogen into glucose-1-phosphate. How will this affect the muscle?
Researchers discover a novel small molecule, 'DesminFix,' that selectively cross-links desmin intermediate filaments in skeletal muscle cells. This cross-linking enhances the mechanical stability and resistance to stretch of the desmin network. How will the activity of 'DesminFix' impact muscle?
Researchers discover a novel small molecule, 'DesminFix,' that selectively cross-links desmin intermediate filaments in skeletal muscle cells. This cross-linking enhances the mechanical stability and resistance to stretch of the desmin network. How will the activity of 'DesminFix' impact muscle?
Imagine a scenario in which scientists are able to selectively disrupt the function of caveolae in skeletal muscle cells using a novel pharmacological agent, 'Caveless.' Caveolae are small, flask-shaped invaginations of the plasma membrane that are enriched in signaling molecules and are thought to play a role in mechanotransduction and membrane repair. So if the invaginations cannot form properly, how would the muscle be impacted?
Imagine a scenario in which scientists are able to selectively disrupt the function of caveolae in skeletal muscle cells using a novel pharmacological agent, 'Caveless.' Caveolae are small, flask-shaped invaginations of the plasma membrane that are enriched in signaling molecules and are thought to play a role in mechanotransduction and membrane repair. So if the invaginations cannot form properly, how would the muscle be impacted?
Consider the use of a novel gene therapy strategy to selectively overexpress the enzyme superoxide dismutase 1 (SOD1) in skeletal muscle fibers. The goal of this therapy is to enhance antioxidant defense and protect against oxidative stress-induced muscle damage. How is this best described?
Consider the use of a novel gene therapy strategy to selectively overexpress the enzyme superoxide dismutase 1 (SOD1) in skeletal muscle fibers. The goal of this therapy is to enhance antioxidant defense and protect against oxidative stress-induced muscle damage. How is this best described?
Researchers are investigating the effects of prolonged microgravity exposure such as during long-duration spaceflight, on skeletal muscle function. They observe a significant decrease in the expression of the transcription factor peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in the muscles of astronauts. They also note the muscles of astronauts exhibit significant dysfunction. Predict the outcome.
Researchers are investigating the effects of prolonged microgravity exposure such as during long-duration spaceflight, on skeletal muscle function. They observe a significant decrease in the expression of the transcription factor peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in the muscles of astronauts. They also note the muscles of astronauts exhibit significant dysfunction. Predict the outcome.
A research team is studying the effects of a novel compound, 'MyoFuse,' on skeletal muscle regeneration following injury. They observe that 'MyoFuse' selectively promotes the fusion of myoblasts into existing muscle fibers, but does not affect the proliferation or differentiation of myoblasts. How will MyoFuse affect muscle regeneration?
A research team is studying the effects of a novel compound, 'MyoFuse,' on skeletal muscle regeneration following injury. They observe that 'MyoFuse' selectively promotes the fusion of myoblasts into existing muscle fibers, but does not affect the proliferation or differentiation of myoblasts. How will MyoFuse affect muscle regeneration?
A researcher engineers a myocyte cell line to express a modified ryanodine receptor (RyR1) that exhibits a 100-fold reduced sensitivity to physiological activators (e.g., Ca2+, ATP). Simultaneously, they introduce a constitutively active, calcium-independent phospholipase C (PLC) isozyme. Assuming that all other excitation-contraction coupling components remain unperturbed, what is the most likely observable consequence?
A researcher engineers a myocyte cell line to express a modified ryanodine receptor (RyR1) that exhibits a 100-fold reduced sensitivity to physiological activators (e.g., Ca2+, ATP). Simultaneously, they introduce a constitutively active, calcium-independent phospholipase C (PLC) isozyme. Assuming that all other excitation-contraction coupling components remain unperturbed, what is the most likely observable consequence?
Consider a scenario where a researcher discovers a novel protein, 'Calsequestrin-X,' within the sarcoplasmic reticulum (SR) of skeletal muscle cells. 'Calsequestrin-X' possesses a unique pH-dependent calcium-binding affinity, exhibiting maximal binding at pH 6.5 and minimal binding at pH 7.4. During intense exercise, the intracellular pH of the muscle fibers decreases to 6.7. What is the likely consequence?
Consider a scenario where a researcher discovers a novel protein, 'Calsequestrin-X,' within the sarcoplasmic reticulum (SR) of skeletal muscle cells. 'Calsequestrin-X' possesses a unique pH-dependent calcium-binding affinity, exhibiting maximal binding at pH 6.5 and minimal binding at pH 7.4. During intense exercise, the intracellular pH of the muscle fibers decreases to 6.7. What is the likely consequence?
A research group discovers a novel compound, 'Myosin-Uncoupler,' that selectively disrupts the allosteric communication between the nucleotide-binding pocket and the actin-binding site on the myosin head. While ATP hydrolysis remains unaffected, the conformational change normally induced by ATP binding and hydrolysis is abolished. What would be the consequence?
A research group discovers a novel compound, 'Myosin-Uncoupler,' that selectively disrupts the allosteric communication between the nucleotide-binding pocket and the actin-binding site on the myosin head. While ATP hydrolysis remains unaffected, the conformational change normally induced by ATP binding and hydrolysis is abolished. What would be the consequence?
Imagine a scenario where a specific mutation in the muscle-specific isoform of creatine kinase (MM-CK) results in a Km for creatine that is increased by three orders of magnitude, while the Vmax remains unchanged. Considering cellular bioenergetics during intense muscle activity, what accurately describes the consequence of the increased Km?
Imagine a scenario where a specific mutation in the muscle-specific isoform of creatine kinase (MM-CK) results in a Km for creatine that is increased by three orders of magnitude, while the Vmax remains unchanged. Considering cellular bioenergetics during intense muscle activity, what accurately describes the consequence of the increased Km?
A researcher discovers a novel mutation in the gene encoding for the dihydropyridine receptor (DHPR) in skeletal muscle cells. This mutation alters a critical charged residue within the voltage-sensing domain (VSD) of DHPR, rendering it completely insensitive to changes in sarcolemma membrane potential. If action potential propagation is still normal, what effect would this mutation have?
A researcher discovers a novel mutation in the gene encoding for the dihydropyridine receptor (DHPR) in skeletal muscle cells. This mutation alters a critical charged residue within the voltage-sensing domain (VSD) of DHPR, rendering it completely insensitive to changes in sarcolemma membrane potential. If action potential propagation is still normal, what effect would this mutation have?
A researcher introduces a novel phosphatase, 'Phospho-X,' into skeletal muscle cells. 'Phospho-X' selectively dephosphorylates phospholamban, a protein that inhibits the SERCA pump. Simultaneously, the researcher introduces a non-functional calcium channel into the T-tubule membrane that otherwise has normal action potential propagation. What is the most likely outcome?
A researcher introduces a novel phosphatase, 'Phospho-X,' into skeletal muscle cells. 'Phospho-X' selectively dephosphorylates phospholamban, a protein that inhibits the SERCA pump. Simultaneously, the researcher introduces a non-functional calcium channel into the T-tubule membrane that otherwise has normal action potential propagation. What is the most likely outcome?
A research team discovers a novel compound, 'MyoTuner,' that selectively alters the kinetics of the myosin power stroke without affecting ATP hydrolysis. Specifically, 'MyoTuner' increases the angle of the power stroke and reduces the rate of ADP release from myosin. Given these modifications, how will 'MyoTuner' affect muscle?
A research team discovers a novel compound, 'MyoTuner,' that selectively alters the kinetics of the myosin power stroke without affecting ATP hydrolysis. Specifically, 'MyoTuner' increases the angle of the power stroke and reduces the rate of ADP release from myosin. Given these modifications, how will 'MyoTuner' affect muscle?
A team of scientists is investigating the effects of a novel drug, 'Relaxacillin,' on smooth muscle contraction. They discover that 'Relaxacillin' selectively enhances the activity of myosin light chain phosphatase (MLCP) while simultaneously inhibiting the RhoA/Rho kinase pathway. Given these combined effects, the most anticipated outcome is:
A team of scientists is investigating the effects of a novel drug, 'Relaxacillin,' on smooth muscle contraction. They discover that 'Relaxacillin' selectively enhances the activity of myosin light chain phosphatase (MLCP) while simultaneously inhibiting the RhoA/Rho kinase pathway. Given these combined effects, the most anticipated outcome is:
Consider a scenario where a mutation in the gene encoding for the troponin complex results in a significant reduction in its affinity for calcium ions, but only at high temperatures (above 40°C). How would elevated temperatures affect excitation?
Consider a scenario where a mutation in the gene encoding for the troponin complex results in a significant reduction in its affinity for calcium ions, but only at high temperatures (above 40°C). How would elevated temperatures affect excitation?
A researcher discovers a novel compound, 'MyoStatBlock,' that selectively inhibits the activity of myostatin propeptide processing enzymes in skeletal muscle cells but has no impact on myostatin gene expression. What would be the outcome?
A researcher discovers a novel compound, 'MyoStatBlock,' that selectively inhibits the activity of myostatin propeptide processing enzymes in skeletal muscle cells but has no impact on myostatin gene expression. What would be the outcome?
In a study, researchers examine the effects of prolonged exposure to a microgravity environment on skeletal muscle function. They observe a significant decrease in the expression of genes involved in mitochondrial fusion and fission. What would happen next?
In a study, researchers examine the effects of prolonged exposure to a microgravity environment on skeletal muscle function. They observe a significant decrease in the expression of genes involved in mitochondrial fusion and fission. What would happen next?
Researchers discover a novel compound, 'T-TubuleMax,' that selectively increases the density of T-tubules in skeletal muscle fibers without altering their diameter or membrane capacitance. How will this directly affect muscle?
Researchers discover a novel compound, 'T-TubuleMax,' that selectively increases the density of T-tubules in skeletal muscle fibers without altering their diameter or membrane capacitance. How will this directly affect muscle?
A researcher is investigating the impact of a novel mutation in the gene encoding for the ryanodine receptor (RyR1) on skeletal muscle function. The mutation results in a constitutively open RyR1 channel. What is the outcome of this mutation?
A researcher is investigating the impact of a novel mutation in the gene encoding for the ryanodine receptor (RyR1) on skeletal muscle function. The mutation results in a constitutively open RyR1 channel. What is the outcome of this mutation?
Consider a scenario where a researcher introduces a non-functional analog of ATP that selectively binds to myosin ATPase but cannot be hydrolyzed. What effect does this cause?
Consider a scenario where a researcher introduces a non-functional analog of ATP that selectively binds to myosin ATPase but cannot be hydrolyzed. What effect does this cause?
A study examines the effects of a novel compound, 'DesminLink,' on skeletal muscle fiber integrity. 'DesminLink' selectively cross-links desmin intermediate filaments at the Z-disc. How will this change muscle?
A study examines the effects of a novel compound, 'DesminLink,' on skeletal muscle fiber integrity. 'DesminLink' selectively cross-links desmin intermediate filaments at the Z-disc. How will this change muscle?
Researchers identify a novel microRNA, 'miR-MuscleRelax,' that specifically targets and inhibits the expression of the gene encoding for the SERCA pump in skeletal muscle cells. How is activity impacted?
Researchers identify a novel microRNA, 'miR-MuscleRelax,' that specifically targets and inhibits the expression of the gene encoding for the SERCA pump in skeletal muscle cells. How is activity impacted?
Consider a scenario where a patient is diagnosed with a rare genetic disorder characterized by a mutation in the gene encoding for the voltage-gated sodium channel Nav1.4, specifically expressed in skeletal muscle. What would happen?
Consider a scenario where a patient is diagnosed with a rare genetic disorder characterized by a mutation in the gene encoding for the voltage-gated sodium channel Nav1.4, specifically expressed in skeletal muscle. What would happen?
Suppose you are testing the impact of overexpressing the enzyme glycogen synthase kinase-3β (GSK-3β) in skeletal muscle fibers. What is the outcome on metabolism?
Suppose you are testing the impact of overexpressing the enzyme glycogen synthase kinase-3β (GSK-3β) in skeletal muscle fibers. What is the outcome on metabolism?
Researchers are investigating the effects of a novel compound, 'MyoProtector,' on skeletal muscle damage following eccentric contractions. They discover that 'MyoProtector' selectively enhances the expression of heat shock proteins (HSPs) in skeletal muscle cells. How will this help the muscle?
Researchers are investigating the effects of a novel compound, 'MyoProtector,' on skeletal muscle damage following eccentric contractions. They discover that 'MyoProtector' selectively enhances the expression of heat shock proteins (HSPs) in skeletal muscle cells. How will this help the muscle?
Consider someone wanting to test the impact of inhibiting the ubiquitin-proteasome system (UPS) in skeletal muscle cells. What happens?
Consider someone wanting to test the impact of inhibiting the ubiquitin-proteasome system (UPS) in skeletal muscle cells. What happens?
A research team is investigating the effects of a novel toxin, 'MyoNecrosin,' on skeletal muscle fibers. They discover that 'MyoNecrosin' selectively disrupts the function of the T-tubules by inhibiting the dihydropyridine receptor (DHPR). How is activity affected?
A research team is investigating the effects of a novel toxin, 'MyoNecrosin,' on skeletal muscle fibers. They discover that 'MyoNecrosin' selectively disrupts the function of the T-tubules by inhibiting the dihydropyridine receptor (DHPR). How is activity affected?
A researcher discovers that the voltage-gated sodium channels in a sample of skeletal muscle cells exhibit a mutation such that, following depolarization, they remain open much longer than normal, what occurs?
A researcher discovers that the voltage-gated sodium channels in a sample of skeletal muscle cells exhibit a mutation such that, following depolarization, they remain open much longer than normal, what occurs?
Consider the application of a drug which hyperpolarizes motor neuron axon terminals at the neuromuscular junction, yet does not prevent action potential propagation down the axon. Predict activity at the NMJ.
Consider the application of a drug which hyperpolarizes motor neuron axon terminals at the neuromuscular junction, yet does not prevent action potential propagation down the axon. Predict activity at the NMJ.
Consider the introduction of a compound that prevents the association of tropomyosin with actin filaments in skeletal muscle. How does the muscle react?
Consider the introduction of a compound that prevents the association of tropomyosin with actin filaments in skeletal muscle. How does the muscle react?
A patient is administrated high levels of a novel drug that selectively blocks M-line proteins within the sarcomere of skeletal muscle cells, but thin filament proteins remain unperturbed. What happens to the muscles?
A patient is administrated high levels of a novel drug that selectively blocks M-line proteins within the sarcomere of skeletal muscle cells, but thin filament proteins remain unperturbed. What happens to the muscles?
A research team discovers a novel protein, 'SarcoCalmodulin,' expressed exclusively in fast-twitch muscle fibers. 'SarcoCalmodulin' exhibits a unique calcium-binding affinity ten times greater than calmodulin that regulates myosin light chain kinase (MLCK). How is a normal muscle contraction altered?
A research team discovers a novel protein, 'SarcoCalmodulin,' expressed exclusively in fast-twitch muscle fibers. 'SarcoCalmodulin' exhibits a unique calcium-binding affinity ten times greater than calmodulin that regulates myosin light chain kinase (MLCK). How is a normal muscle contraction altered?
A hypothetical scenario where a mutation in skeletal muscle cells results in a myosin heavy chain isoform with a significantly reduced duty cycle (the fraction of time myosin is strongly bound to actin during each ATP hydrolysis cycle). Assuming that the number of active crossbridges is unchanged, how will the muscle fiber be affected?
A hypothetical scenario where a mutation in skeletal muscle cells results in a myosin heavy chain isoform with a significantly reduced duty cycle (the fraction of time myosin is strongly bound to actin during each ATP hydrolysis cycle). Assuming that the number of active crossbridges is unchanged, how will the muscle fiber be affected?
Consider you want to test the impact of selectively disrupting the interaction between titin and telethonin at the Z-disc in skeletal muscle sarcomeres. What are the consequences?
Consider you want to test the impact of selectively disrupting the interaction between titin and telethonin at the Z-disc in skeletal muscle sarcomeres. What are the consequences?
Consider a knockout experiment designed to disrupt the function of the costamere complex. What would happen?
Consider a knockout experiment designed to disrupt the function of the costamere complex. What would happen?
Researchers discover a novel signaling pathway in skeletal muscle cells that is activated by a specific myokine, 'MyoKine-Z,' released during high-intensity exercise. 'MyoKine-Z' binds to a receptor on muscle cells and activates a cascade that ultimately inhibits the activity of the mammalian target of rapamycin (mTOR) signaling pathway. How is the cell changed?
Researchers discover a novel signaling pathway in skeletal muscle cells that is activated by a specific myokine, 'MyoKine-Z,' released during high-intensity exercise. 'MyoKine-Z' binds to a receptor on muscle cells and activates a cascade that ultimately inhibits the activity of the mammalian target of rapamycin (mTOR) signaling pathway. How is the cell changed?
A researcher examines the effects of a novel compound, 'MyoAdapt,' on skeletal muscle adaptation to endurance training. They find that 'MyoAdapt' selectively enhances the expression of peroxisome proliferator-activated receptor delta (PPARδ) in skeletal muscle cells. What adaptation should be seen?
A researcher examines the effects of a novel compound, 'MyoAdapt,' on skeletal muscle adaptation to endurance training. They find that 'MyoAdapt' selectively enhances the expression of peroxisome proliferator-activated receptor delta (PPARδ) in skeletal muscle cells. What adaptation should be seen?
Researchers find that a loss-of-function mutation occurs in the gene encoding for the muscle-specific microRNA, miR-206, how does this affect muscle tissue?
Researchers find that a loss-of-function mutation occurs in the gene encoding for the muscle-specific microRNA, miR-206, how does this affect muscle tissue?
Researchers engineer a constitutively active form of calcineurin specifically in slow-twitch muscle fibers. Concurrently, they administer a compound that blocks nuclear import of NFAT. What happens?
Researchers engineer a constitutively active form of calcineurin specifically in slow-twitch muscle fibers. Concurrently, they administer a compound that blocks nuclear import of NFAT. What happens?
Scientists test the effect of selectively inhibiting the enzyme histone deacetylase 4 (HDAC4) in skeletal muscle cells using a small molecule inhibitor. How does the state of histone acetylation change?
Scientists test the effect of selectively inhibiting the enzyme histone deacetylase 4 (HDAC4) in skeletal muscle cells using a small molecule inhibitor. How does the state of histone acetylation change?
Scientists create a transgenic mouse expressing a mutant form of the enzyme AMP-activated protein kinase (AMPK) that is insensitive to activation by AMP. How will muscle metabolism react to this?
Scientists create a transgenic mouse expressing a mutant form of the enzyme AMP-activated protein kinase (AMPK) that is insensitive to activation by AMP. How will muscle metabolism react to this?
Researchers discover that the extracellular matrix protein fibronectin is selectively degraded by a novel matrix metalloproteinase (MMP) in skeletal muscle tissue with otherwise normal components. What happens?
Researchers discover that the extracellular matrix protein fibronectin is selectively degraded by a novel matrix metalloproteinase (MMP) in skeletal muscle tissue with otherwise normal components. What happens?
Researchers identify a peptide which selectively activates the receptor tyrosine kinase MuSK at the neuromuscular junction (NMJ) without acetylcholine esterase inhibitors. Predict the outcome.
Researchers identify a peptide which selectively activates the receptor tyrosine kinase MuSK at the neuromuscular junction (NMJ) without acetylcholine esterase inhibitors. Predict the outcome.
Researchers discover a compound called 'Tropomodulin-X'. 'Tropomodulin-X' selectively disrupts the capping and stabilization of the pointed ends of actin filaments within skeletal muscle sarcomeres without changes to the Z-disk. What occurs?
Researchers discover a compound called 'Tropomodulin-X'. 'Tropomodulin-X' selectively disrupts the capping and stabilization of the pointed ends of actin filaments within skeletal muscle sarcomeres without changes to the Z-disk. What occurs?
Scientists want to test the impact of selectively downregulating the expression of the chloride channel ClC-1 in skeletal muscle cells. How is the normal action potential altered?
Scientists want to test the impact of selectively downregulating the expression of the chloride channel ClC-1 in skeletal muscle cells. How is the normal action potential altered?
A researcher discovers a novel myokine, 'MyoStretch,' that is released from skeletal muscle cells under conditions of high mechanical load. 'MyoStretch' acts on neighboring muscle cells to increase their expression of the enzyme lysyl oxidase (LOX), without changes to titin. How do the muscles respond?
A researcher discovers a novel myokine, 'MyoStretch,' that is released from skeletal muscle cells under conditions of high mechanical load. 'MyoStretch' acts on neighboring muscle cells to increase their expression of the enzyme lysyl oxidase (LOX), without changes to titin. How do the muscles respond?
A research team discovers a peptide that selectively blocks the interaction between filamin and the integrin receptors within the costameres of skeletal muscle cells. How do muscle fibers react to mechanical load?
A research team discovers a peptide that selectively blocks the interaction between filamin and the integrin receptors within the costameres of skeletal muscle cells. How do muscle fibers react to mechanical load?
A researcher engineers a novel competitive inhibitor which impairs the binding of calcium to parvalbumin within fast-twitch skeletal muscle fibers. As action potential frequency is increased, and calcium dynamics are followed, which observation is most likely?
A researcher engineers a novel competitive inhibitor which impairs the binding of calcium to parvalbumin within fast-twitch skeletal muscle fibers. As action potential frequency is increased, and calcium dynamics are followed, which observation is most likely?
Consider a novel gene therapy technique that effectively delivers a short-hairpin RNA (shRNA) construct specifically targeting the mRNA encoding for the dihydropyridine receptor (DHPR) in skeletal muscle cells. What alterations follow action potential propagation?
Consider a novel gene therapy technique that effectively delivers a short-hairpin RNA (shRNA) construct specifically targeting the mRNA encoding for the dihydropyridine receptor (DHPR) in skeletal muscle cells. What alterations follow action potential propagation?
A research team is investigating the effects of a novel compound, 'MyoBalance,' on skeletal muscle homeostasis. They find that 'MyoBalance' selectively inhibits the activity of the FOXO transcription factors in skeletal muscle cells. In the presence of starvation, how is glucose uptake and metabolism?
A research team is investigating the effects of a novel compound, 'MyoBalance,' on skeletal muscle homeostasis. They find that 'MyoBalance' selectively inhibits the activity of the FOXO transcription factors in skeletal muscle cells. In the presence of starvation, how is glucose uptake and metabolism?
In a meticulously controlled experiment involving isolated skeletal muscle fibers, researchers apply a novel compound, 'CelerityBoost,' designed to selectively enhance the rate of action potential propagation along the sarcolemma without altering the resting membrane potential or ion channel kinetics. Following CelerityBoost application, which of the subsequent electrophysiological changes would be anticipated?
In a meticulously controlled experiment involving isolated skeletal muscle fibers, researchers apply a novel compound, 'CelerityBoost,' designed to selectively enhance the rate of action potential propagation along the sarcolemma without altering the resting membrane potential or ion channel kinetics. Following CelerityBoost application, which of the subsequent electrophysiological changes would be anticipated?
Consider a scenario where a researcher introduces a gain-of-function mutation in the gene encoding for the muscle-specific isoform of glycogen phosphorylase (MyoPhos). This mutation results in a MyoPhos enzyme with significantly reduced sensitivity to allosteric inhibition by ATP and glucose-6-phosphate, while maintaining normal catalytic activity. In an isolated muscle fiber preparation stimulated to contract, which of the subsequent metabolic alterations would most likely be observed?
Consider a scenario where a researcher introduces a gain-of-function mutation in the gene encoding for the muscle-specific isoform of glycogen phosphorylase (MyoPhos). This mutation results in a MyoPhos enzyme with significantly reduced sensitivity to allosteric inhibition by ATP and glucose-6-phosphate, while maintaining normal catalytic activity. In an isolated muscle fiber preparation stimulated to contract, which of the subsequent metabolic alterations would most likely be observed?
Researchers discover a novel peptide, 'Stabilin-Z,' that selectively binds to and stabilizes the closed conformation of voltage-gated sodium channels in skeletal muscle sarcolemma. When Stabilin-Z is applied to isolated muscle fibers, which alteration will be directly observed during action potential generation?
Researchers discover a novel peptide, 'Stabilin-Z,' that selectively binds to and stabilizes the closed conformation of voltage-gated sodium channels in skeletal muscle sarcolemma. When Stabilin-Z is applied to isolated muscle fibers, which alteration will be directly observed during action potential generation?
In a study on skeletal muscle plasticity, researchers use CRISPR-Cas9 technology to selectively knock out the gene encoding for the small nuclear RNA (snRNA) responsible for splicing a specific exon in the mRNA transcript of the chloride channel ClC-1. This exon encodes a critical domain for channel trafficking to the sarcolemma. What electrophysiological observation correctly identifies a post-transcriptional alteration?
In a study on skeletal muscle plasticity, researchers use CRISPR-Cas9 technology to selectively knock out the gene encoding for the small nuclear RNA (snRNA) responsible for splicing a specific exon in the mRNA transcript of the chloride channel ClC-1. This exon encodes a critical domain for channel trafficking to the sarcolemma. What electrophysiological observation correctly identifies a post-transcriptional alteration?
A researcher is investigating the effects of a novel synthetic molecule, 'MyoTune,' on the force-frequency relationship in isolated mammalian skeletal muscle fibers. 'MyoTune' selectively and reversibly modifies the kinetics of calcium binding to troponin C (TnC), such that it increases the on-rate ($k_{on}$) for calcium binding but proportionally decreases the off-rate ($k_{off}$). Accounting only for these parameter changes, which of the subsequent alterations in contractile function would be anticipated?
A researcher is investigating the effects of a novel synthetic molecule, 'MyoTune,' on the force-frequency relationship in isolated mammalian skeletal muscle fibers. 'MyoTune' selectively and reversibly modifies the kinetics of calcium binding to troponin C (TnC), such that it increases the on-rate ($k_{on}$) for calcium binding but proportionally decreases the off-rate ($k_{off}$). Accounting only for these parameter changes, which of the subsequent alterations in contractile function would be anticipated?
Flashcards
Muscle Tissue
Muscle Tissue
Nearly half of the body's mass that transforms chemical energy (ATP) into mechanical energy to exert force
Skeletal muscles
Skeletal muscles
Attached to bones and skin. Elongated cells called muscle fibers.
Cardiac muscle
Cardiac muscle
Found only in the heart, striated, and involuntary. It can contract without nervous system stimulation
Smooth muscle
Smooth muscle
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Excitability of muscle tissue
Excitability of muscle tissue
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Contractility of muscle tissue
Contractility of muscle tissue
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Extensibility of muscle tissue
Extensibility of muscle tissue
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Elasticity of muscle tissue
Elasticity of muscle tissue
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Functions of muscles
Functions of muscles
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Skeletal muscle supply
Skeletal muscle supply
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Epimysium
Epimysium
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Perimysium
Perimysium
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Endomysium
Endomysium
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Sarcolemma
Sarcolemma
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Sarcoplasm
Sarcoplasm
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Neuromuscular Junction (NMJ)
Neuromuscular Junction (NMJ)
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Acetylcholine (ACh)
Acetylcholine (ACh)
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Acetylcholinesterase
Acetylcholinesterase
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Muscle Twitch
Muscle Twitch
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Single stimulus response
Single stimulus response
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Recruitment
Recruitment
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Maximal Stimulus
Maximal Stimulus
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Recruitment size principle
Recruitment size principle
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Isotonic Contractions
Isotonic Contractions
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Isometric Contractions
Isometric Contractions
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Muscle Tone
Muscle Tone
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Creatine Phosphate Energy
Creatine Phosphate Energy
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Anaerobic Respiration
Anaerobic Respiration
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Motor Unit
Motor Unit
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Skeletal Muscle: Connective Tissue Sheaths
Skeletal Muscle: Connective Tissue Sheaths
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Muscle fibers
Muscle fibers
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Myofilaments
Myofilaments
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Sarcomere
Sarcomere
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Thick Filaments
Thick Filaments
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Thin Filaments
Thin Filaments
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Z disc
Z disc
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Thick Filaments Composition
Thick Filaments Composition
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Thin Filaments Composition
Thin Filaments Composition
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Sarcoplasmic Reticulum (SR)
Sarcoplasmic Reticulum (SR)
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T Tubules
T Tubules
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Sliding Filament Model
Sliding Filament Model
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Contract a Skeletal Muscle
Contract a Skeletal Muscle
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Skeletal Muscle Nerve Stimulus
Skeletal Muscle Nerve Stimulus
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Neuromuscular Junction Formation
Neuromuscular Junction Formation
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Nerve Impulse at NMJ
Nerve Impulse at NMJ
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ACh Actions
ACh Actions
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Action Potential Definition
Action Potential Definition
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Role of Acetylcholine
Role of Acetylcholine
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Resting Membrane Potential
Resting Membrane Potential
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Extracellular Sodium Ion (Na+)
Extracellular Sodium Ion (Na+)
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Intracellular Potassium Ion (K+)
Intracellular Potassium Ion (K+)
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Sarcolemma Impermeability
Sarcolemma Impermeability
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Action Potential
Action Potential
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Depolarization
Depolarization
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Repolarization
Repolarization
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Refractory Period
Refractory Period
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Excitation-Contraction Coupling
Excitation-Contraction Coupling
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Tropomyosin
Tropomyosin
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Troponin
Troponin
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Repolarization
Repolarization
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Latent Period
Latent Period
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Incomplete Tetanus
Incomplete Tetanus
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Complete tetanus
Complete tetanus
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Threshold Stimulus
Threshold Stimulus
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Motor Unit Summation
Motor Unit Summation
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Treppe (Staircase Effect)
Treppe (Staircase Effect)
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Treppe
Treppe
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Force of muscle contraction
Force of muscle contraction
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Staircase
Staircase
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Muscle Fatigue
Muscle Fatigue
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Extracellular Na+ in Resting Potential
Extracellular Na+ in Resting Potential
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Intracellular K+ in Resting Potential
Intracellular K+ in Resting Potential
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Depolarization Definition
Depolarization Definition
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Action Potential Repolarization
Action Potential Repolarization
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Potassium's Role in Repolarization
Potassium's Role in Repolarization
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Neuromuscular Junction
Neuromuscular Junction
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Excitation-Contraction Coupling phases
Excitation-Contraction Coupling phases
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Role of Calcium in Muscle Contraction
Role of Calcium in Muscle Contraction
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Function of Tropomyosin
Function of Tropomyosin
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Troponin's Role
Troponin's Role
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Muscle Twitch Phases
Muscle Twitch Phases
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Latent Period in Muscle Twitch
Latent Period in Muscle Twitch
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Contraction Period
Contraction Period
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Relaxation Period
Relaxation Period
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Graded Muscle Responses
Graded Muscle Responses
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Isotonic Contractions: Key Types
Isotonic Contractions: Key Types
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Concentric Contractions
Concentric Contractions
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Treppe Effect Explanation
Treppe Effect Explanation
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Threshold Stimulus Definition
Threshold Stimulus Definition
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Force of Contraction: Stimulation Strength
Force of Contraction: Stimulation Strength
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Study Notes
- Muscle tissue makes up nearly half of the body's mass.
- Muscle tissue transforms chemical energy (ATP) into directed mechanical energy to exert force.
- There are three types of muscle tissue which are skeletal, cardiac, and smooth.
- Myo, mys, and sarco are prefixes for muscle.
- Skeletal and smooth muscle cells are elongated and are called muscle fibers.
- Muscle contraction depends on two kinds of myofilaments – actin and myosin.
- Muscle types differ in structure, location, function, and means of activation.
Types of Muscle Tissue
- Skeletal muscles are organs attached to bones and skin.
- Skeletal muscle cells are elongated and called muscle fibers.
- Skeletal muscles are striated (striped).
- Skeletal muscles are voluntary (i.e., conscious control).
- Skeletal muscles contract rapidly, tire easily, and are powerful.
- Skeletal muscles require nervous system stimulation.
- Cardiac muscle is only in the heart and makes up the bulk of the heart walls.
- Cardiac muscle is striated.
- Cardiac muscle can contract without nervous system stimulation.
- Cardiac muscle is involuntary.
- More details on cardiac muscle is in Chapter 18
- Smooth muscle is in the walls of hollow organs, such as the stomach, urinary bladder, and airways.
- Smooth muscle is not striated.
- Smooth muscle can contract without nervous system stimulation.
- Smooth muscle is involuntary, such as when digesting food.
- Peristalsis is muscle contraction that allows food to move from one compartment to another in the GI tract.
Special Characteristics of Muscle Tissue
- Excitability (responsiveness or irritability) is the ability to receive and respond to stimuli.
- Contractility is the ability to shorten forcibly when stimulated.
- Extensibility is the ability to be stretched.
- Elasticity is the ability to recoil to resting length.
Muscle Functions
- Muscle tissue has four main functions.
- Movement of bones or fluids, such as blood.
- Skeletal muscles facilitate all locomotion.
- Cardiac muscle is responsible for coursing the blood through the body.
- Smooth muscle helps maintain blood pressure and squeezes or propels substances through organs.
- Maintaining posture and body position.
- Stabilizing joints.
- Heat generation, especially by skeletal muscle.
- Muscles protect organs, form valves, control pupil size, and cause "goosebumps".
Skeletal Muscle
- Each muscle is served by one artery, one nerve, and one or more veins.
- Nerves and vessels enter/exit near the central part and branch out along connective tissue sheaths.
- Every skeletal muscle fiber is supplied by a nerve ending that controls its activity.
- Contracting fibers require continuous delivery of oxygen and nutrients via arteries.
- Wastes must be removed via veins.
- Skeletal muscles require a huge amount of nutrients and oxygen and generate a large amount of waste.
Skeletal Muscle: Connective Tissue Sheaths
- Connective tissue sheaths support cells and reinforce the whole muscle.
- The sheaths extend from external to internal.
- Epimysium is dense irregular connective tissue surrounding the entire muscle and may blend with fascia.
- Perimysium is fibrous connective tissue surrounding fascicles (groups of muscle fibers).
- Endomysium is fine areolar connective tissue surrounding each muscle fiber.
Skeletal Muscle: Attachments
- Muscles attach in at least two places.
- The insertion is attached to the movable bone.
- The origin is attached to the immovable bone, which is less movable.
Microscopic Anatomy of A Skeletal Muscle Fiber
- Skeletal muscle fibers are long, cylindrical cells.
- They are 10 to 100 µm in diameter and up to 30 cm long.
- Skeletal muscle fibers have multiple peripheral nuclei.
- Sarcolemma is the plasma membrane of a muscle cell.
- Sarcoplasm is the cytoplasm of a muscle cell.
- Glycosomes store glycogen, and myoglobin stores O2.
- Modified structures include myofibrils, sarcoplasmic reticulum, and T tubules.
Myofibrils
- Myofibrils are densely packed, rodlike elements.
- They make up ~80% of cell volume.
- Myofibrils contain sarcomeres, which are contractile units.
- Sarcomeres contain myofilaments.
- Myofibrils exhibit striations, which are perfectly aligned repeating series of dark A bands and light I bands.
Striations
- The H zone is the lighter region in the midsection of the dark A band where filaments do not overlap.
- The M line is a line of protein myomesin that bisects the H zone.
- The Z disc (line) is a coin-shaped sheet of proteins in the midline of the light I band that anchors thin filaments and connects myofibrils to one another.
- Thick filaments run the entire length of an A band.
- Thin filaments run the length of the I band and partway into the A band.
- A sarcomere is the region between two successive Z discs.
Sarcomere
- Sarcomeres are the smallest contractile units, or functional units, of a muscle fiber.
- Sarcomeres align along the myofibril like boxcars of a train.
- Each sarcomere contains an A band with ½ I band at each end.
- Sarcomeres are composed of thick and thin myofilaments made of contractile proteins.
Myofibril Banding Pattern
- The orderly arrangement of actin and myosin myofilaments within sarcomeres.
- Actin myofilaments are thin filaments.
- Actin myofilaments extend across the I band and partway into the A band.
- Actin myofilaments are anchored to Z discs.
- Myosin myofilaments are thick filaments.
- Myosin myofilaments extend the length of the A band.
- Myosin myofilaments are connected at the M line.
Ultrastructure of Thick Filament
- Thick filaments are composed of the protein myosin.
- The thick filament is composed of 2 heavy and four light polypeptide chains.
- Myosin tails contain 2 interwoven, heavy polypeptide chains.
- Myosin heads contain 2 smaller, light polypeptide chains that act as cross bridges during contraction.
- Myosin heads have binding sites for actin of thin filaments, ATP, and ATPase enzymes.
Ultrastructure of Thin Filament
- The thin filament is a twisted double strand of fibrous protein.
- The F actin consists of G (globular) actin subunits.
- G actin has active sites for myosin head attachment during contraction.
- Tropomyosin and troponin are regulatory proteins bound to actin.
Sarcoplasmic Reticulum (SR)
- An SR is a network of smooth endoplasmic reticulum surrounding each myofibril.
- Most run longitudinally.
- Pairs of terminal cisternae form perpendicular cross channels.
- SR functions in the regulation of intracellular Ca2+ levels.
- SR stores and releases Ca2+.
T Tubules
- T tubules are continuations of the sarcolemma.
- The lumen is continuous with extracellular space.
- T tubules increase muscle fiber's surface area.
- T tubules penetrate the cell's interior at each A band-I band junction.
- T tubules associate with paired terminal cisterns to form triads that encircle each sarcomere.
Triad Relationships
- T tubules conduct impulses deep into muscle fiber in every sarcomere.
- Integral proteins protrude into the intermembrane space from the T tubule and SR cistern membranes and act as voltage sensors.
- SR foot proteins are gated channels that regulate Ca2+ release from the SR cisterns.
Sliding Filament Model of Contraction
- The sliding filament model of contraction generates force.
- It does not necessarily cause shortening of the fiber.
- Shortening occurs when the tension generated by cross bridges on thin filaments exceeds the forces opposing shortening.
- In the relaxed state, thin and thick filaments overlap only at the ends of the A band.
- During contraction, thin filaments slide past thick filaments, and actin and myosin overlap more.
- Upon stimulation, myosin heads bind to actin, and sliding begins.
- Each myosin head binds and detaches several times during contraction.
- Myosin heads act like a ratchet to generate tension and propel the thin filaments to the center of the sarcomere.
- As this event occurs throughout the sarcomeres, the muscle shortens.
Physiology of Skeletal Muscle Fibers
- Skeletal muscle to contract must:
- Be activated at the neuromuscular junction
- Have nervous system stimulation
- Generate an action potential in sarcolemma
- Have excitation-contraction coupling
- Action potential is propagated along the sarcolemma
- Intracellular Ca2+ levels must rise briefly
The Nerve Stimulus and Events at the Neuromuscular Junction
- Skeletal muscles are stimulated by somatic motor neurons.
- Axons of motor neurons travel from the central nervous system via nerves to skeletal muscle.
- Each axon forms several branches as it enters a muscle.
- Each axon ending forms a neuromuscular junction with a single muscle fiber.
- There is only one neuromuscular junction per muscle fiber.
Neuromuscular Junction (NMJ)
- The neuromuscular junction is situated midway along the length of the muscle fiber.
- The axon terminal and muscle fiber are separated by a gel-filled space called the synaptic cleft.
- Synaptic vesicles of the axon terminal contain the neurotransmitter acetylcholine (ACh).
- Junctional folds of the sarcolemma contain ACh receptors.
- The NMJ includes axon terminals, the synaptic cleft, and junctional folds.
Events at the Neuromuscular Junction
- A nerve impulse arrives at the axon terminal, and ACh is released into the synaptic cleft.
- ACh diffuses across the cleft and binds with receptors on the sarcolemma, causing electrical events that generate an action potential.
- Voltage-regulated calcium channels open and allow Ca2+ to enter the axon.
- Ca2+ inside the axon terminal causes axonal vesicles to fuse with the axonal membrane and releases ACh into the synaptic cleft via exocytosis
- ACh diffuses across the synaptic cleft to ACh receptors on the sarcolemma, initiating an action potential in the muscle.
Destruction of Acetylcholine
- ACh effects are quickly terminated by the enzyme acetylcholinesterase in the synaptic cleft.
- Acetylcholinesterase breaks down ACh to acetic acid and choline.
- This prevents continued muscle fiber contraction in the absence of additional stimulation.
Generation of an Action Potential
- A transient depolarization event includes polarity reversal of sarcolemma, or nerve cell membrane, and propagation of an action potential along the membrane.
- The resting sarcolemma is polarized with voltage across the membrane.
- An action potential is caused by changes in electrical charges.
- It occurs in three steps:
- End plate potential
- Depolarization
- Repolarization
- The outside (extracellular) face of a polarized sarcolemma is positive, while the inside face is negative.
- This difference in charge creates the resting membrane potential.
- The predominant extracellular ion is Na+.
- The predominant intracellular ion is K+.
- The sarcolemma is relatively impermeable to both ions.
Generation of an Action Potential Across the Sarcolemma
- End plate potential causes local depolarization.
- ACh binding opens chemically (ligand) gated ion channels.
- Simultaneous diffusion of Na+ (inward) and K+ (outward) occurs.
- More Na+ diffuses in, so the interior of the sarcolemma becomes less negative.
- Local depolarization = end plate potential.
Events in Generation of an Action Potential
- Depolarization generates and propagates an action potential (AP).
- The end plate potential spreads to adjacent membrane areas.
- Voltage-gated Na+ channels open.
- Na+ influx decreases membrane voltage towards a critical voltage called the threshold.
- If the threshold is reached, AP is initiated.
- Once initiated, it is unstoppable leading to muscle fiber contraction.
- AP spreads across the sarcolemma.
- Voltage-gated Na+ channels open in the adjacent patch, causing it to depolarize to threshold.
- An axonal terminal of a motor neuron releases ACh, causing a patch of the sarcolemma to become permeable to Na+ when sodium channels open.
- Na+ enters the cell, decreasing the resting potential, which causes depolarization.
- If the stimulus is strong enough, an action potential is initiated.
- Polarity reversal of the initial patch of sarcolemma changes the permeability of the adjacent patch.
- Voltage-regulated Na+ channels open in the adjacent patch, causing it to depolarize.
- Therefore, the action potential travels rapidly along the sarcolemma, eventually resulting in muscle contraction.
Events in Generation of an Action Potential
- Repolarization restores electrical conditions of the resting membrane potential.
- Na+ channels close and voltage-gated K+ channels open.
- K+ efflux rapidly restores resting polarity.
- The fiber cannot be stimulated in a refractory period until repolarization is complete.
- Ionic conditions of resting state are restored by the Na+-K+ pump.
- Immediately after the depolarization wave passes, the sarcolemma permeability changes.
- Na+ channels close, and K+ channels open.
- K+ diffuses from the cell, restoring the electrical polarity of the sarcolemma.
- Repolarization occurs in the same direction as depolarization, and must occur before the muscle can be stimulated again, which is known as the refractory period.
- The ionic concentration of the resting state is restored by the Na+-K+ pump.
Role of Acetylcholine (Ach)
- ACh binds its receptors at the motor end plate.
- Binding opens chemically (ligand) gated channels.
- Na+ and K+ diffuse in and out, therefore the interior of the sarcolemma becomes less negative.
- This event is called depolarization.
Excitation-Contraction (E-C) Coupling
- Occurs when events that transmit AP along the sarcolemma lead to the sliding of myofilaments.
- The AP is brief and ends before contraction.
- Causes a rise in intracellular Ca2+, which leads to contraction.
- A latent period occurs which is the time when E-C coupling events occur.
- It occurs between AP initiation and the beginning of contraction.
- Once generated, the action potential is propagated along the sarcolemma and travels down the T tubules.
- The action potential then triggers Ca2+ release from terminal cisternae.
Events of Excitation-Contraction (E-C) Coupling
- The AP is propagated along the sarcolemma to the T tubules.
- Voltage-sensitive proteins stimulate Ca2+ release from the SR.
- Ca2+ is necessary for contraction.
Channels Involved in Initiating Muscle Contraction
- A nerve impulse reaches the axon terminal, and voltage-gated calcium channels open.
- ACh is released to the synaptic cleft.
- ACh binds to its receptors on the sarcolemma, opening ligand-gated Na+ and K+ channels, causing an end plate potential.
- Voltage-gated Na+ channels open, allowing the AP to propagate.
- Voltage-sensitive proteins in T tubules change shape, stimulating the SR to release Ca2+ to cytosol.
Role of Calcium (Ca2+) in Contraction
- At low intracellular Ca2+ concentration, tropomyosin blocks active sites on actin.
- Myosin heads cannot attach to actin, so the muscle fiber is relaxed.
- At higher intracellular Ca2+ concentrations, Ca2+ binds to troponin.
- Troponin changes shape and moves tropomyosin away from myosin-binding sites.
- Myosin heads bind to actin, causing sarcomere shortening and muscle contraction.
- When nervous stimulation ceases, Ca2+ is pumped back into the SR, and contraction ends.
- At low intracellular Ca2+ concentration:
- Tropomyosin blocks the binding sites on actin
- Myosin cross bridges cannot attach to binding sites on actin
- The relaxed state of the muscle is enforced
- At higher intracellular Ca2+ concentrations:
- Additional calcium binds to troponin (inactive troponin binds two Ca2+)
- Calcium-activated troponin binds an additional two Ca2+ at a separate regulatory site
- Calcium-activated troponin undergoes a conformational change.
- The change moves tropomyosin away from actin’s binding sites.
- Ca2+ binds to troponin and causes:
- The blocking action of tropomyosin to cease
- Actin active binding sites to be exposed
Cross Bridge Cycle
- The cross bridge cycle continues as long as the Ca2+ signal and adequate ATP are present.
- Cross bridge formation occurs when a high-energy myosin head attaches to a thin filament.
- A working (power) stroke happens when the myosin head pivots and pulls the thin filament toward the M line.
- Cross bridge detachment occurs when ATP attaches to the myosin head, and the cross bridge detaches.
- "Cocking" of the myosin head happens when energy from hydrolysis of ATP cocks the myosin head into a high-energy state.
- Myosin cross bridges alternately attach and detach
- Thin filaments move toward the center of the sarcomere
- Hydrolysis of ATP powers this cycling process
- Ca2+ is removed into the SR, tropomyosin blockage is restored, and the muscle fiber relaxes
- Myosin head can now bind and cycle.
- This permits contraction by sliding of the thin filaments by the myosin cross bridges to begin.
Homeostatic Imbalance
- Rigor mortis occurs due to homeostatic imbalance.
- Cross bridge detachment requires ATP.
- 3–4 hours after death, muscles begin to stiffen with weak rigidity at 12 hours post mortem.
- Dying cells take in calcium -> cross bridge formation.
- No ATP is generated to break cross bridges.
Review Principles of Muscle Mechanics
- The same principles apply to the contraction of a single fiber and a whole muscle.
- Contraction produces muscle tension, which is the force exerted on a load or object to be moved.
- Contraction may or may not shorten the muscle.
- Isometric contraction does not shorten muscles; muscle tension increases but does not exceed the load.
- Isotonic contraction shortens muscles because muscle tension exceeds the load.
- The force and duration of contraction vary in response to stimuli of different frequencies and intensities.
- Contraction of muscle fibers (cells) and muscles (organs) is similar.
- The two types of muscle contractions are:
- Isometric contraction – increasing muscle tension; the muscle does not shorten during contraction
- Isotonic contraction – decreasing muscle length; the muscle shortens during contraction
Motor Unit: The Nerve-Muscle Functional Unit
- Each muscle is served by at least one motor nerve.
- A motor nerve contains axons of up to hundreds of motor neurons.
- Axons branch into terminals, each of which creates a neuromuscular junction (NMJ) with a single muscle fiber.
- A motor unit is a motor neuron and all (four to several hundred) muscle fibers it supplies.
- A smaller number of muscle fibers leads to finer control.
- Muscle fibers from a motor unit spread throughout the muscle, so a single motor unit causes a weak contraction of the entire muscle.
- Motor units in a muscle usually contract asynchronously, which helps prevent fatigue.
- A motor unit is a motor neuron and all the muscle fibers it supplies.
- The number of muscle fibers per motor unit can vary from four to several hundred.
- Muscles that control fine movements, such as fingers and eyes, have small motor units.
- Large weight-bearing muscles, such as thighs and hips, have large motor units.
- Muscle fibers from a motor unit are spread throughout the muscle, therefore contraction of a single motor unit causes weak contraction of the entire muscle.
Muscle Twitch
- A muscle twitch is a motor unit's response to a single action potential of its motor neuron.
- It is the simplest contraction observable in the lab and is recorded as a myogram.
- A muscle twitch is the response of a muscle to a single, brief threshold stimulus
- The three phases of a muscle twitch are:
- Latent period – first few milliseconds after stimulation when excitation-contraction coupling is taking place
- Period of contraction – cross bridges actively form and the muscle shortens
- Period of relaxation – Ca2+ is reabsorbed into the SR, and muscle tension goes to zero
Muscle Twitch
- There are three phases of a muscle twitch.
- The latent period is the time of the excitation-contraction coupling, but there is no muscle tension.
- The period of contraction is the time of cross bridge formation, and tension increases.
- The period of relaxation is the time of Ca2+ reentry into the SR, and tension declines to zero.
- Muscle contracts faster than it relaxes.
- https://www.youtube.com/watch?v=I80Xx7pA9hQLinks to an external site.
Muscle Twitch Comparisons
- Different strength and duration of twitches are due to variations in the metabolic properties and enzymes between muscles.
- A muscle twitch only occurs in the lab or during neuromuscular problems; normal muscle contraction is smooth.
Graded Muscle Responses
- Graded muscle responses are variations in the strength of contraction for different demands.
- Graded muscle responses are required for proper control of skeletal movement.
- Responses are graded by changing the frequency or strength of stimulation.
- A single stimulus results in a single contractile response—a muscle twitch.
- Graded muscle responses are variations in the degree of muscle contraction and are required for proper control of skeletal movement.
- Responses are graded by changing the frequency of stimulation or changing the strength of the stimulus.
Response to Change in Stimulus Frequency
- Wave (temporal) summation happens when there is an increased stimulus frequency.
- This occurs when the muscle does not completely relax between stimuli, and the second contraction is of greater force.
- Additional Ca2+ release with the second stimulus stimulates more shortening, producing smooth, continuous contractions
- A further increase in stimulus frequency leads to unfused (incomplete) tetanus.
- If stimuli are given quickly enough, the muscle reaches maximal tension, resulting in fused (complete) tetany
- Smooth, sustained contraction happens when there is no muscle relaxation leading to muscle fatigue and the muscle cannot contract, with zero tension.
- https://www.youtube.com/watch?v=qTt_2oPI2kkLinks to an external site.
- A single stimulus results in a single contractile response, otherwise known as a muscle twitch.
- Frequently delivered stimuli, where the muscle does not have time to completely relax, increases contractile force, known as wave summation.
- More rapidly delivered stimuli result in incomplete tetanus.
- Stimuli that are given quickly enough result in complete tetanus.
Response to Change in Stimulus Strength
- Recruitment (multiple motor unit summation) controls the force of contraction.
Threshold Stimuli
- Subthreshold stimuli have no observable contractions.
- A threshold stimulus is the stimulus strength causing the first observable muscle contraction.
- A maximal stimulus is the strongest stimulus that increases contractile force.
- Muscle contracts more vigorously as stimulus strength increases above threshold.
- Contraction force is precisely controlled by recruitment, which activates more and more muscle fibers.
- Beyond a maximal stimulus, there is no increase in the force of contraction.
- Recruitment works on the size principle, such that motor units with the smallest muscle fibers are recruited first.
- Motor units with larger and larger fibers are recruited as stimulus intensity increases, and the largest motor units are activated only for the most powerful contractions.
- Threshold stimulus is the stimulus strength at which the first observable muscle contraction occurs
- Beyond threshold, muscle contracts more vigorously as stimulus strength is increased
Isotonic Contractions
- A muscle changes in length and moves a load.
- Thin filaments slide during all isotonic contractions which are either concentric or eccentric.
- Concentric contractions shorten the muscle and do work.
- Eccentric contractions generate force as the muscle lengthens.
- In isometric contractions, the load is greater than the tension the muscle can develop.
- Tension increases to the muscle's capacity, but the muscle neither shortens nor lengthens.
- Cross bridges generate force but do not move actin filaments.
- https://www.youtube.com/watch?v=PHTUlwCnCe8Links to an external site.
- https://www.youtube.com/watch?v=pbXML3m2hSELinks to an external site.
- With isotonic contractions, the muscle changes in length, decreasing the angle of the joint, and moves the load.
- The two types of isotonic contractions are concentric and eccentric.
- Concentric contractions shorten the muscle and does work.
Isometric Contractions
- With isometric contractions, tension increases to the muscle’s capacity, but the muscle neither shortens nor lengthens
- This will occur if the load is greater than the tension the muscle is able to develop
Muscle Tone
- Muscle tone is a constant, slightly contracted state of all muscles.
- It is due to spinal reflexes.
- Groups of motor units are alternately activated in response to input from stretch receptors in muscles.
- Muscle tone keeps muscles firm, healthy, and ready to respond.
- Muscle tone is the constant, slightly contracted state of all muscles, which does not produce active movements;
- Keeps the muscles firm, healthy, and ready to respond to stimulus
Force of Muscle Contraction
- The force of contraction depends on the number of cross bridges attached, which is affected by the number of muscle fibers stimulated (recruitment), the relative size of fibers, frequency of stimulation, and degree of muscle stretch.
- As more muscle fibers are recruited (as more are stimulated), this leads to more force.
- A larger relative size of fibers, where muscles are bulkier and cells undergo hypertrophy, leads to more force.
- A higher frequency of stimulation leads to a shorter time for the transfer of tension to noncontractile components, giving more force.
- The maximum length-tension relationship happens when muscle fibers are at 80–120% of their normal resting length, leading to more force.
- The force of contraction is affected by:
- The number of muscle fibers contracting, where the more motor fibers in a muscle, the stronger the contraction
- The relative size of the muscle, where the bulkier the muscle, the greater its strength
- The degree of muscle stretch, where muscles contract strongest when muscle fibers are 80-120% of their normal resting length
Muscle Metabolism: Energy for Contraction
- ATP is the only source used directly for contractile activities.
- ATP is needed to move and detach cross bridges, calcium pumps in the SR, and return Na+ & K+ after excitation-contraction coupling.
- Available stores of ATP are depleted in 4–6 seconds.
- ATP is regenerated by direct phosphorylation of ADP by creatine phosphate (CP), the anaerobic pathway(glycolysis à lactic acid), or aerobic respiration.
Anaerobic Pathway
- Glycolysis does not require oxygen.
- Glucose is degraded to 2 pyruvic acid molecules.
- Normally, pyruvic acid molecules enter the mitochondria for aerobic respiration.
- At 70% of maximum contractile activity, bulging muscles compress blood vessels, oxygen delivery is impaired, and pyruvic acid is converted to lactic acid.
- Lactic acid diffuses into the bloodstream.
- Lactic acid is used as fuel by the liver, kidneys, and heart.
- Lactic acid is also converted back into pyruvic acid or glucose by the liver.
- Anaerobic respiration yields only 5% as much ATP as aerobic respiration but produces ATP 2½ times faster.
Aerobic Pathway
- The aerobic pathway produces 95% of ATP during rest and light-to-moderate exercise and is slow.
- It involves a series of chemical reactions that require oxygen and occur in the mitochondria.
- Glucose is broken into CO2, H2O, and a large amount of ATP.
- Fuels used are stored glycogen, then bloodborne glucose, pyruvic acid from glycolysis, and free fatty acids.
Muscle Fatigue
- Muscle fatigue occurs when the muscle is in a state of physiological inability to contract.
- Muscle fatigue occurs when:
- ATP production fails to keep pace with ATP use
- There is a relative deficit of ATP, causing contractures
- Lactic acid accumulates in the muscle
- Ionic imbalances are present
- Intense exercise produces rapid muscle fatigue, and this is followed by rapid recovery
- Na+-K+ pumps cannot restore ionic balances quickly enough
- SR is damaged, and Ca2+ regulation is disrupted
Heat Production During Muscle Activity
- Only 40% of the energy released in muscle activity is useful as work.
- The remaining 60% is given off as heat.
- Dangerous heat levels are prevented by radiation of heat from the skin and sweating.
Action Potential and Polarized Sarcolemma
- The outside (extracellular) face is positive, while the inside face is negative.
- This difference in charge is the resting membrane potential.
- The predominant extracellular ion is Na+.
- The predominant intracellular ion is K+.
- The sarcolemma is relatively impermeable to both ions.
Action Potential Depolarization and Generation
- An axonal terminal of a motor neuron releases ACh, causing a patch of the sarcolemma to become permeable to Na+ when sodium channels open.
- Na+ enters the cell, decreasing the resting potential and causing depolarization.
- The stimulus must be strong enough for an action potential to be initiated.
Action Potential Propagation
- Polarity reversal of the initial patch of sarcolemma changes the permeability of the adjacent patch.
- Voltage-regulated Na+ channels then open in the adjacent patch causing it to depolarize.
- Therefore, the action potential travels rapidly along the sarcolemma.
- Once initiated, the action potential is unstoppable and ultimately results in the contraction of a muscle.
Action Potential Repolarization
- The sarcolemma permeability changes immediately after the depolarization wave passes.
- Na+ channels close, and K+ channels open.
- K+ diffuses from the cell, restoring the electrical polarity of the sarcolemma.
- Repolarization occurs in the same direction as depolarization and must occur before the muscle can be stimulated again (refractory period).
- The ionic concentration of the resting state is restored by the Na+-K+ pump.
Excitation-Contraction Coupling
- Once generated, the action potential is propagated along the sarcolemma and travels down the T tubules.
- Action potential triggers Ca2+ release from terminal cisternae.
- Ca2+ binds to troponin, which causes the blocking action of tropomyosin to cease, therefore actin active binding sites are exposed.
- Myosin cross bridges alternately attach and detach
- Thin filaments move toward the center of the sarcomere.
- Hydrolysis of ATP powers this cycling process.
- Ca2+ is later removed into the SR, tropomyosin blockage is restored, and the muscle fiber relaxes.
Role of Ionic Calcium in Contraction
- At low intracellular Ca2+ concentration:
- Tropomyosin blocks the binding sites on actin.
- Myosin cross bridges cannot attach to binding sites on actin.
- The muscle is in a relaxed state.
- At higher intracellular Ca2+ concentrations, additional calcium binds to troponin, with inactive troponin binding two Ca2+.
- Calcium-activated troponin binds an additional two Ca2+ at a separate regulatory site.
- The calcium-activated troponin undergoes a conformational change.
- This change moves tropomyosin away from actin’s binding sites, permitting contraction and sliding of thin filaments via myosin cross bridges.
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