Muscle Tissue Types

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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?

  • 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?

  • 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'?

  • 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'?

<p>Increased intracellular calcium concentration and prolonged muscle contraction. (A)</p> Signup and view all the answers

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?

<p>Decreased maximal force production and increased shortening velocity (C)</p> Signup and view all the answers

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?

<p>Decreased resting sarcomere length and decreased passive force (B)</p> Signup and view all the answers

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?

<p>Depolarization of the sarcolemma and uncontrolled muscle contraction leading to rigor mortis-like state (D)</p> Signup and view all the answers

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?

<p>Decreased glycolytic capacity, increased oxidative capacity, and increased fatigue resistance (D)</p> Signup and view all the answers

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?

<p>Increased expression of 'miR-X' (A)</p> Signup and view all the answers

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?

<p>Decreased calcium influx through voltage-gated calcium channels, leading to reduced sarcoplasmic reticulum calcium release (C)</p> Signup and view all the answers

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?

<p>Low immunogenicity and high vascularization potential of the construct to promote cell survival and tissue regeneration (C)</p> Signup and view all the answers

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?

<p>Decreased calcium sensitivity of muscle contraction due to reduced affinity of troponin for actin (B)</p> Signup and view all the answers

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?

<p>Increased maximal shortening velocity and increased power output during rapid contractions (D)</p> Signup and view all the answers

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?

<p>Increased degradation of sarcomeric proteins and impaired structural support for muscle fibers (C)</p> Signup and view all the answers

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?

<p>Increased muscle fiber atrophy and impaired regenerative capacity following injury (B)</p> Signup and view all the answers

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?

<p>A decrease in the maximal force-generating capacity of the muscle. (A)</p> Signup and view all the answers

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?

<p>Increased muscle protein synthesis and hypertrophy due to enhanced mTOR signaling. (B)</p> Signup and view all the answers

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?

<p>Disrupted alignment of actin filaments and reduced force-generating capacity. (B)</p> Signup and view all the answers

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'?

<p>Activation of matrix metalloproteinases (MMPs) and ECM remodeling. (D)</p> Signup and view all the answers

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?

<p>Decreased glucose uptake due to impaired insulin signaling and reduced GLUT4 expression. (B)</p> Signup and view all the answers

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?

<p>Failed activation of ryanodine receptors (RyR1) and impaired calcium release from the sarcoplasmic reticulum, resulting in muscle weakness. (B)</p> Signup and view all the answers

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?

<p>Spontaneous and uncontrolled muscle contractions, even in the absence of calcium. (A)</p> Signup and view all the answers

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?

<p>Decreased sarcomere number in parallel, leading to muscle atrophy. (A)</p> Signup and view all the answers

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?

<p>Reduced ATP hydrolysis by myosin ATPase and increased cross-bridge detachment. (C)</p> Signup and view all the answers

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?

<p>Shortening of titin and reduced overlap between actin and myosin filaments at optimal length. (B)</p> Signup and view all the answers

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?

<p>Increased activity of citrate synthase (CS) and enhanced oxidative capacity in endurance athletes. (D)</p> Signup and view all the answers

Consider someone who has McArdle's disease, where there is a deficiency in muscle glycogen phosphorylase. How is their muscle function most directly affected?

<p>Inability to break down muscle glycogen during intense exercise, leading to exercise intolerance and muscle cramps. (C)</p> Signup and view all the answers

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?

<p>Dantrolene, a ryanodine receptor antagonist. (B)</p> Signup and view all the answers

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?

<p>Fast contraction velocity and high power output, but low resistance to fatigue. (B)</p> Signup and view all the answers

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?

<p>Impaired propagation of action potentials along the sarcolemma, preventing muscle fiber activation. (B)</p> Signup and view all the answers

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?

<p>Impaired lateral alignment of adjacent myofibrils, leading to compromised force transmission (D)</p> Signup and view all the answers

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?

<p>Sustained depolarization of the motor endplate, leading to receptor desensitization and eventual neuromuscular blockade (B)</p> Signup and view all the answers

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?

<p>Increased refractory period and reduced excitability of the muscle fiber (A)</p> Signup and view all the answers

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?

<p>Shift in the force-frequency relationship towards lower frequencies (C)</p> Signup and view all the answers

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?

<p>Complete uncoupling of sarcolemma depolarization from sarcoplasmic reticulum calcium release (C)</p> Signup and view all the answers

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?

<p>Inhibition of smooth muscle contraction due to impaired myosin phosphorylation (A)</p> Signup and view all the answers

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?

<p>Impaired lateral force transmission from muscle fibers to the extracellular matrix, leading to reduced overall muscle strength (B)</p> Signup and view all the answers

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?

<p>Accumulation of misfolded proteins and impaired muscle fiber function (A)</p> Signup and view all the answers

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?

<p>Increased fatigue resistance during prolonged submaximal exercise (C)</p> Signup and view all the answers

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?

<p>Disrupted sarcomere assembly and impaired myofibril organization (C)</p> Signup and view all the answers

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?

<p>Incomplete differentiation of myoblasts into mature muscle fibers (D)</p> Signup and view all the answers

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?

<p>Potentiation of calcium release from the sarcoplasmic reticulum via IP3-mediated mechanisms (A)</p> Signup and view all the answers

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?

<p>Disruption of myofibril alignment and weakened lateral force transmission (D)</p> Signup and view all the answers

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?

<p>Increased expression of profibrotic genes and extracellular matrix deposition (D)</p> Signup and view all the answers

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?

<p>Selective degradation of sarcomeric proteins and muscle atrophy (B)</p> Signup and view all the answers

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?

<p>Decreased amplitude and shortened duration of calcium transients due to reduced calcium storage capacity (A)</p> Signup and view all the answers

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?

<p>Enhanced mitochondrial biogenesis and improved capacity for fatty acid oxidation (C)</p> Signup and view all the answers

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?

<p>Reactivation of previously silenced genes and reversal of age-related decline in muscle function (A)</p> Signup and view all the answers

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?

<p>Impaired alignment of myofibrils and compromised force transmission (C)</p> Signup and view all the answers

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?

<p>Increased self-renewal capacity of satellite cells and enhanced muscle regenerative potential (B)</p> Signup and view all the answers

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?

<p>Decreased expression of GLUT4 and impaired glucose uptake (C)</p> Signup and view all the answers

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?

<p>Impaired calcium sequestration into the sarcoplasmic reticulum and prolonged muscle contraction (C)</p> Signup and view all the answers

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?

<p>Reduced oxidative stress resistance and increased protein degradation (D)</p> Signup and view all the answers

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?

<p>Reduced force production and impaired contractile velocity (D)</p> Signup and view all the answers

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?

<p>Reduced calcium sensitivity of the contractile machinery and impaired cross-bridge cycling (A)</p> Signup and view all the answers

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?

<p>Disrupted thin filament length regulation and impaired force generation (A)</p> Signup and view all the answers

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?

<p>Increased expression of voltage-gated calcium channels and enhanced excitation-contraction coupling efficiency. (C)</p> Signup and view all the answers

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?

<p>Impaired muscle relaxation due to reduced calcium uptake by the sarcoplasmic reticulum (A)</p> Signup and view all the answers

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?

<p>Marked muscle hypertrophy and increased muscle fiber size (D)</p> Signup and view all the answers

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?

<p>Impaired propagation of action potentials into the muscle fiber interior and reduced calcium release (D)</p> Signup and view all the answers

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?

<p>Increased speed of contraction but reduced force production (C)</p> Signup and view all the answers

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?

<p>Reduced autophagic flux and impaired clearance of damaged organelles (C)</p> Signup and view all the answers

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?

<p>Increased reliance on glucose uptake from the bloodstream during exercise (B)</p> Signup and view all the answers

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?

<p>Delayed repolarization due to persistent sodium influx prolonging the depolarized state. (D)</p> Signup and view all the answers

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'?

<p>Decreased muscle fiber excitability and increased threshold for action potential initiation. (D)</p> Signup and view all the answers

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?

<p>Prolonged depolarization of the post-synaptic membrane leading to desensitization and muscle weakness. (C)</p> Signup and view all the answers

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?

<p>Decreased amplitude of end-plate potentials (EPPs) and reduced muscle fiber depolarization. (B)</p> Signup and view all the answers

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'?

<p>Spastic paralysis due to a reduction in inhibitory neurotransmitter release at inhibitory neuromuscular junctions. (C)</p> Signup and view all the answers

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?

<p>Decreased muscle contractility and increased susceptibility to fatigue. (C)</p> Signup and view all the answers

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?

<p>Increased internal load opposing muscle shortening, resulting in reduced velocity. (A)</p> Signup and view all the answers

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?

<p>Increased peak force production and faster relaxation kinetics due to enhanced calcium reuptake into the sarcoplasmic reticulum. (A)</p> Signup and view all the answers

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?

<p>Decreased maximal force production at saturating calcium concentrations due to impaired actin-myosin interaction. (C)</p> Signup and view all the answers

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?

<p>Impaired transmission of force along the myofibril and reduced maximal force production. (A)</p> Signup and view all the answers

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?

<p>Enhanced differentiation of satellite cells into myoblasts and increased fusion with existing myofibers. (C)</p> Signup and view all the answers

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?

<p>Impaired glycogen synthesis and increased insulin resistance due to reduced glucose transport. (A)</p> Signup and view all the answers

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?

<p>Abolished acetylcholine release from the motor neuron-like cell, preventing muscle fiber-like cell activation. (D)</p> Signup and view all the answers

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?

<p>Disrupted sarcomere organization and impaired force transmission, leading to muscle weakness. (D)</p> Signup and view all the answers

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?

<p>Improved protein folding and reduced aggregation, leading to enhanced muscle function under stress. (D)</p> Signup and view all the answers

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?

<p>Enhanced endurance capacity and improved resistance to fatigue during prolonged exercise. (B)</p> Signup and view all the answers

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?

<p>Spontaneous muscle contractions and increased susceptibility to malignant hyperthermia. (A)</p> Signup and view all the answers

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?

<p>Enhanced satellite cell activation and improved muscle regeneration capacity. (A)</p> Signup and view all the answers

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?

<p>Impaired force transmission to the extracellular matrix and increased susceptibility to muscle damage. (B)</p> Signup and view all the answers

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:

<p>Reduced passive tension and increased susceptibility to sarcomere over-extension. (D)</p> Signup and view all the answers

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?

<p>Reduced expression of ion channel proteins and impaired action potential propagation. (A)</p> Signup and view all the answers

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?

<p>Impaired differentiation of myoblasts into mature myofibers and reduced muscle mass. (D)</p> Signup and view all the answers

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?

<p>Improved synaptic transmission and enhanced muscle force production due to increased AChR density. (B)</p> Signup and view all the answers

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?

<p>Impaired glycogen breakdown and reduced energy production during intense exercise. (B)</p> Signup and view all the answers

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?

<p>Improved force transmission and decreased susceptibility to mechanical stress-induced injury. (C)</p> Signup and view all the answers

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?

<p>Impaired mechanotransduction and reduced ability to repair membrane damage. (B)</p> Signup and view all the answers

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?

<p>Improved resistance to oxidative stress and enhanced muscle function. (B)</p> Signup and view all the answers

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.

<p>Impaired mitochondrial function and reduced endurance capacity. (C)</p> Signup and view all the answers

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?

<p>Enhanced repair of damaged muscle fibers and increased muscle fiber size. (B)</p> Signup and view all the answers

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?

<p>Severely blunted excitation-contraction coupling, with minimal calcium release despite PLC activation, necessitating supraphysiological stimulation for contraction. (B)</p> Signup and view all the answers

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?

<p>Increased calcium buffering within the SR, leading to enhanced calcium release during subsequent action potentials, thus potentiating muscle contraction. (D)</p> Signup and view all the answers

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?

<p>Uncoupling disrupts the power stroke mechanism, leading to a stall in actin filament sliding and a severe reduction in muscle force generation because energized myosin head cannot properly interact with actin. (B)</p> Signup and view all the answers

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?

<p>Accelerated onset of muscle fatigue and impaired peak power output are most likely, due to the inability to buffer ATP levels effectively at physiological creatine concentrations. (B)</p> Signup and view all the answers

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?

<p>Complete abrogation of excitation-contraction coupling because mutated DHPR cannot undergo conformational change. (C)</p> Signup and view all the answers

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?

<p>An increase in the rate of sarcoplasmic reticulum calcium reuptake and faster muscle relaxation. (C)</p> Signup and view all the answers

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?

<p>Increase in muscle force production and a decrease in shortening velocity. (D)</p> Signup and view all the answers

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:

<p>A synergistic relaxation of smooth muscle due to decreased myosin light chain phosphorylation and reduced calcium sensitivity. (D)</p> Signup and view all the answers

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?

<p>A decrease in maximal force production, particularly at high stimulation frequencies. (D)</p> Signup and view all the answers

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?

<p>An increase in muscle fiber size due to enhanced protein synthesis. (B)</p> Signup and view all the answers

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?

<p>A decrease in muscle fiber size and strength due to impaired mitochondrial function. (D)</p> Signup and view all the answers

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?

<p>An increase in the efficiency of excitation-contraction coupling and force production. (D)</p> Signup and view all the answers

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?

<p>A sustained increase in intracellular calcium concentration, leading to chronic muscle contraction and damage. (C)</p> Signup and view all the answers

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?

<p>A sustained muscle contraction due to irreversible binding of myosin to actin. (B)</p> Signup and view all the answers

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?

<p>An increase in muscle fiber stiffness and resistance to stretch. (D)</p> Signup and view all the answers

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?

<p>An increase in intracellular calcium concentration and sustained muscle contraction. (A)</p> Signup and view all the answers

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?

<p>A decrease in the excitability of skeletal muscle fibers and impaired action potential propagation. (D)</p> Signup and view all the answers

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?

<p>A decrease in glycogen synthesis and glucose uptake. (D)</p> Signup and view all the answers

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?

<p>A decrease in muscle fiber damage and improved recovery following eccentric contractions. (B)</p> Signup and view all the answers

Consider someone wanting to test the impact of inhibiting the ubiquitin-proteasome system (UPS) in skeletal muscle cells. What happens?

<p>An accumulation of damaged proteins and impaired muscle function. (C)</p> Signup and view all the answers

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?

<p>A decrease in calcium release from the sarcoplasmic reticulum and impaired muscle contraction. (C)</p> Signup and view all the answers

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?

<p>The muscle fibers become hyperexcitable, potentially leading to tetanic contractions. (A)</p> Signup and view all the answers

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.

<p>Decreased acetylcholine release due to reduced calcium influx. (B)</p> Signup and view all the answers

Consider the introduction of a compound that prevents the association of tropomyosin with actin filaments in skeletal muscle. How does the muscle react?

<p>A sustained contraction due to uninhibited myosin binding. (A)</p> Signup and view all the answers

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?

<p>Disrupted sarcomere organization and reduced force transmission. (D)</p> Signup and view all the answers

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?

<p>Increased twitch duration due to the greater calcium sensitivity of myosin light chain kinase (MLCK). (A)</p> Signup and view all the answers

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?

<p>Decreased isometric force generation and increased shortening velocity. (B)</p> Signup and view all the answers

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?

<p>Decreased sarcomere stability and increased susceptibility to stretch-induced damage. (C)</p> Signup and view all the answers

Consider a knockout experiment designed to disrupt the function of the costamere complex. What would happen?

<p>Increased susceptibility to mechanical stress-induced damage and muscular dystrophy-like phenotype. (D)</p> Signup and view all the answers

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?

<p>A decrease in muscle protein synthesis and atrophy. (D)</p> Signup and view all the answers

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?

<p>An increase in muscle fiber oxidative capacity and endurance performance. (A)</p> Signup and view all the answers

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?

<p>Impaired muscle regeneration and increased fibrosis. (B)</p> Signup and view all the answers

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?

<p>No significant change in muscle fiber type composition or function. (D)</p> Signup and view all the answers

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?

<p>Increased expression of genes involved in muscle hypertrophy and strength. (B)</p> Signup and view all the answers

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?

<p>Impaired glucose uptake and fatty acid oxidation in response to exercise. (C)</p> Signup and view all the answers

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?

<p>Disrupted muscle fiber alignment, increased fibrosis, and impaired muscle function. (B)</p> Signup and view all the answers

Researchers identify a peptide which selectively activates the receptor tyrosine kinase MuSK at the neuromuscular junction (NMJ) without acetylcholine esterase inhibitors. Predict the outcome.

<p>Increased acetylcholine receptor (AChR) clustering at the NMJ. (B)</p> Signup and view all the answers

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?

<p>Decreased thin filament length, sarcomere instability, and reduced force production. (D)</p> Signup and view all the answers

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?

<p>Increased excitability and susceptibility to myotonia (prolonged muscle contraction). (D)</p> Signup and view all the answers

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?

<p>Increased collagen cross-linking, increased muscle stiffness, and improved force transmission. (B)</p> Signup and view all the answers

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?

<p>Disrupted force transmission and cell signaling in response to mechanical stress, leading to muscle weakness and increased susceptibility to injury. (A)</p> Signup and view all the answers

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?

<p>A prolongation of the duration of intracellular calcium transients and slower relaxation. (A)</p> Signup and view all the answers

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?

<p>Impaired excitation-contraction coupling leading to muscle weakness or paralysis. (B)</p> Signup and view all the answers

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?

<p>Decreased autophagy and decreased protein degradation. (B)</p> Signup and view all the answers

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?

<p>A reduction in the duration of the absolute refractory period, facilitating higher frequency stimulation. (B)</p> Signup and view all the answers

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?

<p>Elevated rates of glycogenolysis and glucose utilization, even under conditions of high ATP and glucose-6-phosphate levels. (B)</p> Signup and view all the answers

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?

<p>A reduction in the rate of rise (dV/dt) of the action potential during the depolarization phase. (B)</p> Signup and view all the answers

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?

<p>Extended periods of high membrane excitability after initial stimulation. (C)</p> Signup and view all the answers

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?

<p>An increase in the slope of the force-frequency relationship, indicative of enhanced calcium sensitivity. (D)</p> Signup and view all the answers

Flashcards

Muscle Tissue

Nearly half of the body's mass that transforms chemical energy (ATP) into mechanical energy to exert force

Skeletal muscles

Attached to bones and skin. Elongated cells called muscle fibers.

Cardiac muscle

Found only in the heart, striated, and involuntary. It can contract without nervous system stimulation

Smooth muscle

Found in the walls of hollow organs, involuntary, and not striated. Food goes from one compartment to another in your GI tract. AKA Peristalsis

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Excitability of muscle tissue

Ability to receive and respond to stimuli.

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Contractility of muscle tissue

Ability to shorten forcibly when stimulated

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Extensibility of muscle tissue

Ability to be stretched.

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Elasticity of muscle tissue

Ability to recoil to resting length

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Functions of muscles

Movement of bones or fluids, maintaining posture, stabilizing joints, heat generation, protecting organs, forms valves, controls pupil size, causes "goosebumps"

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Skeletal muscle supply

Each muscle served by one artery, one nerve, and one or more veins.

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Epimysium

Dense irregular connective tissue surrounding entire muscle

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Perimysium

Fibrous connective tissue surrounding fascicles (groups of muscle fibers)

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Endomysium

Fine areolar connective tissue surrounding each muscle fiber

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Sarcolemma

Plasma membrane

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Sarcoplasm

Cytoplasm of a muscle cell.

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Neuromuscular Junction (NMJ)

Location where a nerve ending controls a skeletal muscle fiber's activity.

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Acetylcholine (ACh)

Stored in the synaptic vesicles, this neurotransmitter is released at the axon terminal.

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Acetylcholinesterase

The enzyme that quickly terminates ACh effects in the synaptic cleft.

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Muscle Twitch

A muscle fiber’s response to a single action potential from its motor neuron.

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Single stimulus response

A single stimulus results in a single contractile response

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Recruitment

Process where the force of contraction is controlled by multiple motor unit summation

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Maximal Stimulus

The strongest stimulus that increases contractile force.

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Recruitment size principle

Motor units with smallest muscle fibers are activated first

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Isotonic Contractions

Contractions where muscle changes in length and moves the load.

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Isometric Contractions

Tension increases to muscles capacity, but muscle neither shortens nor lengthens

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Muscle Tone

Constant, slightly contracted state of all muscles

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Creatine Phosphate Energy

ATP is regenerated by direct phosphorylation of ADP by creatine phosphate (CP)

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Anaerobic Respiration

Generates little ATP but produces ATP 2.5 times faster.

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Motor Unit

A motor neuron and all (four to several hundred) muscle fibers it supplies

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Skeletal Muscle: Connective Tissue Sheaths

Dense irregular connective tissue surrounding entire muscle; may blend with fascia.

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Muscle fibers

Skeletal and smooth muscle cells, known for their elongated shape.

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Myofilaments

Contractile proteins; actin and myosin.

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Sarcomere

The smallest contractile unit of a muscle fiber.

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Thick Filaments

Extend the entire length of an A band.

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Thin Filaments

Extend across the I band and partway into the A band.

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Z disc

Coin-shaped sheet of proteins that anchors thin filaments and connects myofibrils.

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Thick Filaments Composition

Composed of the protein myosin, featuring rodlike tails and globular heads (cross bridges).

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Thin Filaments Composition

Chiefly composed of the protein actin; also contains tropomyosin and troponin.

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Sarcoplasmic Reticulum (SR)

Elaborate, smooth endoplasmic reticulum that surrounds each myofibril and regulates intracellular calcium levels.

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T Tubules

Invaginations of the sarcolemma that conduct impulses to the deepest regions of the muscle cell.

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Sliding Filament Model

The process where myosin heads attach to actin, causing the thin filaments to slide past the thick filaments.

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Contract a Skeletal Muscle

Skeletal muscle must be stimulated by a nerve ending, propagate an electrical current along its sarcolemma, and experience a rise in intracellular Ca2+ levels.

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Skeletal Muscle Nerve Stimulus

Skeletal muscles are stimulated by motor neurons of the somatic nervous system.

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Neuromuscular Junction Formation

Axonal endings with synaptic vesicles that contain acetylcholine (ACh); motor end plate of the sarcolemma with ACh receptors; the synaptic cleft.

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Nerve Impulse at NMJ

Voltage-regulated calcium channels open, allowing Ca2+ to enter the axon, which causes axonal vesicles to fuse with the axonal membrane.

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ACh Actions

ACh is released into the synaptic cleft via exocytosis, diffuses across the cleft to ACh receptors on the sarcolemma, and initiates an action potential in the muscle.

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Action Potential Definition

Transient depolarization event, including polarity reversal of the sarcolemma and propagation of an action potential along the membrane.

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Role of Acetylcholine

ACh binding to its receptors at the motor end plate opens chemically gated channels, allowing Na+ and K+ to diffuse in and out, resulting in depolarization.

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Resting Membrane Potential

Difference in charge across a polarized sarcolemma representing potential energy.

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Extracellular Sodium Ion (Na+)

The predominant extracellular ion that contributes to the positive charge outside the sarcolemma.

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Intracellular Potassium Ion (K+)

The predominant intracellular ion that contributes to the negative charge inside the sarcolemma.

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Sarcolemma Impermeability

The sarcolemma's characteristic that it is difficult for ions to pass through.

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Action Potential

A wave of depolarization that travels along the sarcolemma when a muscle is stimulated.

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Depolarization

Phase where the sarcolemma becomes permeable to sodium ions, leading to a reversal of membrane potential.

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Repolarization

Restoring the sarcolemma to its initial polarized state, with the outside positive and the inside negative.

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Refractory Period

The period after repolarization when a muscle fiber cannot be stimulated.

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Excitation-Contraction Coupling

Links the electrical signal (action potential) to the contraction of the muscle.

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Tropomyosin

A structural protein that blocks myosin binding sites on actin when a muscle is relaxed.

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Troponin

A complex of three regulatory proteins that binds calcium ions, triggering a conformational change that moves tropomyosin.

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Repolarization

Occurs in the direction as depolarization, and must happen again before the muscle can be stimulated

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Latent Period

A brief delay that occurs between the time when the action potential occurs and the start of mechanical contraction.

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Incomplete Tetanus

Rapidly delivered stimuli result in this type of incomplete tetanus.

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Complete tetanus

Stimuli are given quickly enough, this then results

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Threshold Stimulus

The minimum stimulus required to generate an observable muscle contraction.

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Motor Unit Summation

The phenomenon where the force of muscle contraction increases as more motor units are stimulated.

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Treppe (Staircase Effect)

The sequential increase in contraction strength when a muscle is stimulated repeatedly with the same intensity.

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Treppe

Increased contraction in response to multiple stimuli of the same strength

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Force of muscle contraction

The number of muscle fibers contracting, the relative size of the muscle, the degree of muscle stretch

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Staircase

Formed by multiple stimuli of the same strength

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Muscle Fatigue

When the muscle is in a state of physiological inability to contract

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Extracellular Na+ in Resting Potential

The predominant positive ion outside the muscle cell during resting membrane potential.

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Intracellular K+ in Resting Potential

The predominant positive ion inside the muscle cell during resting membrane potential.

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Depolarization Definition

Brief reversal of membrane potential due to Na+ influx.

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Action Potential Repolarization

Process of restoring the resting membrane potential after depolarization.

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Potassium's Role in Repolarization

The ion channels reopen during the excitation phase of a muscle contraction, restoring the initial polarized state.

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Neuromuscular Junction

A junction where the motor neuron communicates to the muscle fiber.

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Excitation-Contraction Coupling phases

Step- by- step process when the electrical signal (action potential) is converted into muscle contraction.

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Role of Calcium in Muscle Contraction

Binds troponin, causing tropomyosin to move and expose myosin-binding sites.

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Function of Tropomyosin

Blocks myosin binding sites on actin when muscle is relaxed.

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Troponin's Role

A protein complex that binds calcium ions, triggering changes in tropomyosin.

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Muscle Twitch Phases

The phases in which a muscle twitch occurs, in response to a single threshold stimulus.

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Latent Period in Muscle Twitch

The initial pause after stimulation when excitation-contraction coupling is occurring.

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Contraction Period

Tension increases cross bridges form.

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Relaxation Period

Calcium reabsorbed and muscle tension goes to zero.

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Graded Muscle Responses

Variations in muscle contraction degree for precise skeletal movements.

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Isotonic Contractions: Key Types

The muscle shortens or lengthens while the load is moved; concentric and eccentric.

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Concentric Contractions

The muscle shortens and does work.

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Treppe Effect Explanation

Increased contraction with repeated stimuli of the same strength.

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Threshold Stimulus Definition

The stimulus strength at which the first observable muscle contraction occurs.

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Force of Contraction: Stimulation Strength

More motor units fire as stimulus strength is increased.

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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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