Muscle Physiology and Membrane Potential
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Questions and Answers

Which type of muscle fatigue is characterized by a fast onset and fast recovery?

  • High frequency fatigue (correct)
  • Metabolic fatigue
  • Chronic fatigue
  • Long duration fatigue

    • What primarily causes a decrease in force development during metabolic fatigue?

  • Improved blood flow to the muscle fibers
  • Reduced Ca2+ release and contractile protein function (correct)
  • Increased sodium levels in muscle fibers
  • Enhanced ATP production in the mitochondria

    • Which of the following substances is known to mitigate metabolic fatigue by affecting Ca2+ dynamics?

  • Sodium bicarbonate
  • Creatine phosphate
  • Lactic acid
  • Caffeine (correct)

    • What is the primary energy source for muscle contraction?

    <p>Adenosine triphosphate (ATP)</p> Signup and view all the answers

    In terms of muscle fatigue, what aspect does 'long duration fatigue' primarily refer to?

    <p>Accumulation of fatigue over extended periods</p> Signup and view all the answers

    What happens to contractile proteins when there is elevated intracellular calcium concentration?

    <p>They undergo damage due to calpain activity.</p> Signup and view all the answers

    Which type of muscle fatigue is characterized by prolonged low-frequency stimulation?

    <p>Long duration fatigue</p> Signup and view all the answers

    In what scenario does eccentric contraction lead to muscle damage?

    <p>Stretching the muscle while contracting during downhill walking.</p> Signup and view all the answers

    Which components of the muscle structure are most likely to be disrupted by high levels of intracellular calcium?

    <p>RyR and DHPR mechanical link.</p> Signup and view all the answers

    What is the normal PK : PNa : PCl ratio observed in muscle cells?

    <p>1 : 0.01 : 2</p> Signup and view all the answers

    What effect does an increase in inorganic phosphate ($Pi$) and magnesium ($Mg^{2+}$) have on contractile function?

    <p>It reduces contractile function.</p> Signup and view all the answers

    How does increased levels of adenosine diphosphate (ADP) and adenosine monophosphate (AMP) affect ryanodine receptor (RyR) opening?

    <p>They compete with ATP for the stimulatory site on RyR, reducing opening.</p> Signup and view all the answers

    What is the role of lactic acid in relation to exercise-induced fatigue as suggested by the information provided?

    <p>Lactic acid has no causal relationship with fatigue.</p> Signup and view all the answers

    Which mechanism does increased magnesium ($Mg^{2+}$) employ to reduce the opening of the DHPR?

    <p>It makes it harder for the DHPR to open RyR.</p> Signup and view all the answers

    What effect does acidosis have on the permeability of chloride channels?

    <p>It decreases the permeability of chloride channels.</p> Signup and view all the answers

    In McArdle's disease, what is the primary reason for quicker fatigue despite no lactate production?

    <p>Deficiency of glycogen phosphorylase.</p> Signup and view all the answers

    What is a consequence of decreased ATP levels on ryanodine receptor (RyR) activity?

    <p>It decreases RyR opening.</p> Signup and view all the answers

    What is the primary function of lactate in the body during and after exercise?

    <p>It stimulates glucose production in the liver.</p> Signup and view all the answers

    What is the main consequence of intense anaerobic exercise on ATP and other metabolites in muscle fibers?

    <p>Decrease in pH and ATP levels</p> Signup and view all the answers

    Which reaction describes the process of converting creatine phosphate to ATP?

    <p>Cr-Phosphate + ADP → ATP + Cr</p> Signup and view all the answers

    What is the role of the sarcoplasmic reticulum (SR) in muscle contraction?

    <p>To release calcium ions needed for muscle contraction</p> Signup and view all the answers

    Which of the following statements is true regarding ATP and its structure?

    <p>ATP consists of adenosine and three phosphate groups</p> Signup and view all the answers

    In aerobic respiration, how many ATP molecules can be generated from one glucose molecule?

    <p>36 ATP</p> Signup and view all the answers

    What triggers the opening of RyR (Ryanodine receptor) calcium release channels in the muscle cells?

    <p>Voltage changes caused by DHPR activation</p> Signup and view all the answers

    Which molecule competes with ATP for binding at certain enzymatic sites due to its similar structure?

    <p>ADP</p> Signup and view all the answers

    What metabolic change primarily occurs during light exercise conditions?

    <p>Increase in phosphate concentration</p> Signup and view all the answers

    Which of the following processes does NOT directly produce ATP?

    <p>Phosphocreatine breakdown</p> Signup and view all the answers

    What happens to ATP levels in muscle fibers during prolonged intense exercise?

    <p>ATP levels decrease significantly</p> Signup and view all the answers

    Match the types of muscle fatigue with their descriptions:

    <p>High frequency fatigue = Characterized by rapid onset and quick recovery ‘Metabolic’ fatigue = Associated with depletion of energy substrates Long duration fatigue = Lasts for days, caused by eccentric damage Low frequency stimulation fatigue = Triggered by stimulation at lower frequencies, e.g., 20 Hz</p> Signup and view all the answers

    Match the calcium-related processes with their effects on muscle function:

    <p>Elevated Ca2+ = Causes damage to contractile proteins High Ca2+ activation of calpains = Severs the link between RyR and DHPR Intracellular Ca2+ overload = Leads to muscle damage during eccentric contractions Ca2+ in the sarcoplasmic reticulum = Regulates the release of calcium for contractions</p> Signup and view all the answers

    Match the PK : PNa : PCl ratios with their corresponding membrane potentials:

    <p>1 : 0.01 : 2 = -88 mV 1 : 0.01 : 1 = -88.4 mV 1 : 0.01 : 0 = -89.3 mV 1 : 0.02 : 1 = Value not provided</p> Signup and view all the answers

    Match the scenarios related to muscle contractions with their effects:

    <p>Walking downhill = Causes eccentric damage leading to fatigue Stretching while contracting = Contributes to increased intracellular Ca2+ Low frequency stimulation (20 Hz) = Causes a form of muscle fatigue High intensity exercise = Can trigger prolonged duration fatigue</p> Signup and view all the answers

    Match the components affected by elevated Ca2+ with their roles in muscle contraction:

    <p>Sarcoplasmic reticulum = Stores calcium ions for muscle contractions RyR = Responsible for calcium release from the sarcoplasmic reticulum DHPR = Facilitates calcium influx during action potential Contractile proteins = Executors of muscle contraction forces</p> Signup and view all the answers

    Match the types of muscle fatigue with their characteristics:

    <p>High frequency fatigue = Fast onset, fast recovery Metabolic fatigue = Decreased Ca2+ release Long duration fatigue = Prolonged low-frequency stimulation Caffeine = Enhances Ca2+ release</p> Signup and view all the answers

    Match the stages of metabolic fatigue with their respective effects:

    <p>Stage A = Initial force decline Stage B = Intermediate force recovery Stage C = Significant force decrease Stage D = Final recovery or exhaustion</p> Signup and view all the answers

    Match the metabolites with their role in causing metabolic fatigue:

    <p>Inorganic phosphate ($Pi$) = Reduces contractile function Adenosine diphosphate (ADP) = Increases ATP consumption Lactic acid = Affects pH levels Calcium ($Ca^{2+}$) = Plays a role in force generation</p> Signup and view all the answers

    Match the components of the muscle fiber with their locations:

    <p>Extracellular space = Outside the muscle fiber Sarcoplasmic reticulum (SR) = Calcium storage Sarcolemma = Muscle fiber membrane Contractile proteins = Generate force during contraction</p> Signup and view all the answers

    Match the energy sources with their characteristics in muscle contraction:

    <p>Creatine phosphate = Quick ATP regeneration Glucose = Primary energy source during exercise Fatty acids = Long-term energy supply Lactic acid = Byproduct of anaerobic metabolism</p> Signup and view all the answers

    Match the following substances with their associated metabolic roles or effects:

    <p>ATP = Primary energy currency in cells ADP = Product of ATP hydrolysis Creatine phosphate = Energy storage molecule for quick ATP regeneration Lactate = Byproduct of anaerobic metabolism</p> Signup and view all the answers

    Match the following energy pathways with their respective characteristics:

    <p>Aerobic respiration = Produces 36 ATP per glucose molecule Anaerobic respiration = Produces 2 ATP per glucose molecule Phosphocreatine breakdown = Provides immediate energy for short bursts Glycolysis = Initial breakdown of glucose without oxygen</p> Signup and view all the answers

    Match the following ATP-related processes with their descriptions:

    <p>ATP hydrolysis = Releases energy for cellular work ADP phosphorylation = Converts ADP back to ATP Creatine phosphate reaction = Replenishes ATP quickly during high-intensity activity Glycolytic pathway = Converts glucose to pyruvate and generates ATP</p> Signup and view all the answers

    Match the following calcium dynamics to their occurence locations:

    <p>Ca2+ release from SR = Occurs during muscle contraction Ca2+ binding to contractile proteins = Facilitates muscle contraction Ca2+ reuptake into SR = Restores muscle relaxation Ca2+ influx through DHPR = Triggers release from SR</p> Signup and view all the answers

    Match the following metabolic changes with the exercise intensity:

    <p>Light exercise = Increased phosphate levels Intense exercise = Elevated lactate and H+ levels Prolonged aerobic exercise = Stable ATP and glycogen levels Interval training = Rapid shifts in ATP and ADP levels</p> Signup and view all the answers

    Match the following ATP derivatives with their synthesis pathways:

    <p>ATP = Generated from glucose and oxygen in mitochondria ADP = Formed from ATP during energy expenditure AMP = Result of further degradation of ADP IMP = Produced from AMP via deamination</p> Signup and view all the answers

    Match the following types of muscle fatigue with their characteristics:

    <p>Metabolic fatigue = Caused by depletion of energy substrates Mechanical fatigue = Relates to the inability to contract Neural fatigue = Inhibits motor neuron signaling Psychological fatigue = Involves CNS and perceived exertion</p> Signup and view all the answers

    Match the following effects of exercise on metabolic state:

    <p>Increased ADP = Signals a need for ATP synthesis Elevated inorganic phosphate ($Pi$) = Impairs contractile function Decreased ATP levels = Leads to muscle fatigue Increased magnesium ($Mg^{2+}$) = May reduce calcium sensitivity</p> Signup and view all the answers

    Match the following cellular structures/functions with their roles:

    <p>Sarcoplasmic reticulum (SR) = Stores and releases calcium T-tubules = Facilitates signal transmission for contraction DHPR = Voltage-sensitive channel involved in calcium entry Contractile proteins = Generate force during muscle contraction</p> Signup and view all the answers

    Match the following ATP-related reactions with their resulting products:

    <p>ATP → ADP + Pi = Release of energy for muscle activity Glucose + 2 ADP + 2 Pi = Produces 2 ATP and 2 lactate Creatine phosphate + ADP = Produces ATP and creatine Glucose + 6 O2 + ADP = Produces 36 ATP through aerobic metabolism</p> Signup and view all the answers

    Match the following metabolic changes with their effects on muscle contraction:

    <p>↑Pi = Decreases contractile function ↑Mg2+ = Makes it harder for DHPR to open RyR ↑ADP = Competes with ATP for RyR binding ↓ATP = Decreases RyR opening</p> Signup and view all the answers

    Match the following substances to their roles in muscle metabolism:

    <p>Lactate = Stimulates glucose production in the liver ADP = Competes with ATP for RyR Mg2+ = Inhibits RyR opening Pi = Reduces free [Ca2+] in the SR</p> Signup and view all the answers

    Match the following ions with their effects on muscle physiology:

    <p>Ca2+ = Involved in muscle contraction Cl- = Permeability decreased by acidosis H+ = Affects pH but has little effect on ECC Mg2+ = Inhibits calcium release</p> Signup and view all the answers

    Match the following diseases or conditions with their characteristics:

    <p>McArdle's disease = Fatigues quickly due to glycogen phosphorylase deficiency Acidosis = Decreases permeability of Cl- channels Higher ADP/AMP = Reduces RyR opening Low ATP = Decreases calcium release from RyR</p> Signup and view all the answers

    Match the metabolic substances to their described effects:

    <p>Lactic acid = Has a relationship with fatigue but not a direct cause ADP = Inhibits RyR opening when elevated Mg2+ = Raises Kd, making it harder for DHPR to function ATP = Necessary for effective RyR opening</p> Signup and view all the answers

    Match the following metabolic products with their origin:

    <p>Lactate = Produced during glycolysis from glucose ATP = Sourced from substrate-level phosphorylation ADP = Generated from ATP usage in muscle Pi = Released during ATP hydrolysis</p> Signup and view all the answers

    Match the following physiological responses with their triggers:

    <p>Increased Pi = Reduces free calcium in SR Increased magnesium = Inhibits DHPR opening of RyR Decreased ATP = Reduces calcium release Increased lactate = Triggers glucose production in liver</p> Signup and view all the answers

    Match the following statements with the correct physiological terms:

    <p>Ca-P forms = Lower free calcium in SR Stimulatory site on RyR = Binding site for ATP Hyperacidosis = Reduces chloride channel activity Glucose metabolism = Produces lactate under anaerobic conditions</p> Signup and view all the answers

    Study Notes

    Muscle Membrane Potential

    • The normal ratio of PK : PNa : PCl is 1 : 0.01 : 2, producing a membrane potential of -88 mV
    • Changing the ratio to 1 : 0.01 : 1 results in a membrane potential of -88.4 mV
    • Changing the ratio further to 1 : 0.01 : 0 results in a membrane potential of -89.3 mV

    Muscle Fatigue

    • High frequency fatigue has a fast onset and fast recovery.
    • ‘Metabolic’ fatigue involves metabolic changes inside the muscle fiber.
    • Long duration fatigue lasts for days and is potentially caused by stretching the muscle while contracting (eccentric damage), raising intracellular Ca2+ levels for too long, or both.
    • Long duration fatigue can occur during activities like walking downhill

    Electron Micrographs of Normal Muscle Sarcomeres

    • Normal muscle sarcomeres exhibit an ordered and uniform array.
    • These structures can be visualized using electron micrographs.

    After Eccentric Contractions

    • Muscle sarcomeres exhibit disruption following eccentric contractions.

    Elevated Ca2+ Causes Damage

    • Elevated Ca2+ levels can damage contractile proteins.
    • High Ca2+ activates calpains, which are Ca2+ dependent proteases, and severs the mechanical link between ryanodine receptors (RyR) and dihydropyridine receptors (DHPR).

    EC Coupling and Muscle Fatigue

    • Interference in any of the excitation-contraction (EC) coupling processes can cause muscle fatigue.

    Stages of Metabolic Fatigue

    • The stages of metabolic fatigue in an intact muscle fiber are labelled from A to D.
    • During metabolic fatigue, less force is produced due to reduced Ca2+ release and decreased force development by contractile proteins.
    • ‘Caffeine’ is used experimentally to stimulate Ca2+ release in muscle fibers.

    Energy Sources for Muscle

    • The energy source for muscle is adenosine triphosphate (ATP).

    Sites of ATP Usage

    • ATP is used in multiple sites within a muscle fiber including the T-tubule, contractile proteins, and the Ca2+ pump of the sarcoplasmic reticulum (SR).

    ATP Utilization

    • ADP and Pi are produced when ATP is hydrolysed.
    • The enzyme myoadenylate deaminase catalyses the conversion of AMP to IMP, which is further converted to adenosine.

    ATP Regeneration

    • ATP is regenerated from glucose and oxygen in mitochondria through aerobic respiration.
    • ATP can also be regenerated from glucose alone via anaerobic respiration, which produces lactate and hydrogen ions.

    Metabolic Changes During Exercise

    • During light exercise, phosphate levels increase inside the muscle fiber.
    • During intense exercise, levels of phosphate, lactate, hydrogen ions, magnesium, ADP, and AMP increase, while ATP, pH, glycogen, and creatine levels decrease.

    Metabolic Changes and Effects

    • Increased phosphate and magnesium levels decrease contractile function.
    • Elevated phosphate reduces free Ca2+ levels by forming calcium phosphate.
    • Increased hydrogen ions (decreased pH) have little effect on overall EC coupling.
    • Increased ADP and AMP compete with ATP for the stimulatory site on RyR, reducing Ca2+ release.
    • Increased magnesium levels make it harder for the DHPR to open RyR.
    • Decreased ATP levels decrease RyR opening.

    Lactate and Fatigue

    • The myth that lactate causes fatigue originated in 1929.
    • Just because there is a correlation between fatigue and lactate levels does not mean that lactate causes fatigue.
    • Lactate stimulates glucose production in the liver, acts as a readily diffusible fuel for the heart and brain, and is involved in the release of human growth hormone.
    • In McArdle's disease, patients lack glycogen phosphorylate and therefore cannot produce lactate, yet they still experience fatigue.

    Acidosis and Muscle Fatigue

    • Acidosis decreases the permeability of chloride channels, contributing to fatigue.
    • This may explain why fatigue occurs sooner during anaerobic metabolism.

    DHPR-RyR Coupling

    • Dihydropyridine receptors (DHPR) are voltage-sensitive molecules located in the T-tubules.
    • They act as a stimulatory site for RyR, triggering Ca2+ release from the SR.
    • Increased ADP and AMP inhibit RyR activity.
    • Increased magnesium levels also increase RyR activity.

    Summary of Metabolic Changes and Effects

    • Increased phosphate and magnesium levels decrease contractile function.
    • Phosphate reduces the free [Ca2+] in the SR by forming CaP.
    • Elevated H+ (ie. decreased pH) has little effect on overall EC coupling.
    • Increased ADP and AMP compete with ATP for the stimulatory site on RyR, reducing RyR opening and Ca2+ release.
    • Elevated Mg2+ makes it harder for the DHPR to open RyR.
    • Reduced ATP levels decrease RyR opening.

    Membrane Potential

    • Normal ratio of PK : PNa : PCl is 1:0.01:2 => -88mV
    • Changing that ratio to 1:0.01:1 => -88.4mV
    • Changing the ratio to 1:0.01:0 => -89.3mV

    Muscle Fatigue

    • High Frequency Fatigue
      • Fast onset
      • Fast recovery
    • Metabolic Fatigue
      • Involves reduced force production due to less calcium release and or decreased force production by contractile proteins
    • Long Duration Fatigue
      • Lasts days
      • Related to stretching the muscle while contracting (eccentric damage - e.g walking downhill)
      • Low frequency stimulation (e.g. 20Hz)
      • Raising the intracellular calcium concentration too much or for too long
      • Muscle damage caused by eccentric contractions (stretching muscles while contracting)
      • Calcium and stretch-induced damage

    Electron Micrographs of Muscle Sarcomeres

    • Ordered and uniform array of components

    Electron Micrographs of Normal Muscle Sarcomeres After Eccentric Contractions

    • Disruption of muscle sarcomeres

    Calcium and Muscle Damage

    • Elevated calcium causes damage
    • Extracellular space
    • Sarcolemma
    • Intracellular space
    • Contractile proteins
    • Calcium damage to contractile proteins
    • Sarcoplasmic reticulum (SR)
    • High calcium concentration activates calpains (calcium-dependent protease)
    • Calpains sever the mechanical link between the ryanodine receptor (RyR) and the dihydropyridine receptor (DHPR)

    Muscle Fatigue and EC Coupling

    • Interference in any of the excitation-contraction (EC) coupling processes causes fatigue

    Stages of Metabolic Fatigue in an Intact Muscle Fiber

    • Stage A: initial force production
    • Stage B: force declines due to decrease in calcium release and/or reduced force production by contractile proteins
    • Stage C: force declines further, caffeine can reverse this effect (suggests the drop in force is due to a decrease in calcium release)
    • Stage D: no force production, caffeine has no effect (suggests the drop in force is due to a decrease in force production by the contractile proteins)

    ATP Usage

    • T-tubule
    • SR
    • Contractile proteins
    • Calcium pump

    ATP Utilization

    • ATP binds to magnesium (Mg2+)
    • MgATP

    Sites of ATP Usage

    • T-tubule
    • Contractile proteins
    • Calcium pumps
    • Sarcoplasmic reticulum (SR)

    ATP: Adenosine Triphosphate

    • Short term:
      • ATP → ADP + Phosphate
      • Creatine phosphate (Cr-P) + ADP → ATP + Cr
    • Longer term:
      • Glucose and oxygen in mitochondria: GLUCOSE + 6 O2 + ADP + 36 Pi  36 ATP (‘Aerobic’)
      • Glucose alone: GLUCOSE + 2 ADP + 2 Pi  2 ATP + 2 LACTATE + 2 H+ (‘Anaerobic’)

    Metabolic Changes in an Intact Muscle Fiber

    • Light exercise: Increased phosphate
    • Intense exercise (anaerobic):
      • Increased phosphate, lactate, H+, Mg2+, ADP, AMP
      • Decreased ATP, pH, glycogen, Cr

    Metabolic Changes (cont)

    • Increased Pi (phosphate) and Mg2+ decrease contractile function
    • Increased phosphate reduces the free calcium concentration in the SR (e.g., calcium phosphate calcium-Pi forms).
    • Increased H+ (i.e., decreased pH) has little effect on overall EC coupling.
    • Increased ADP and AMP compete with ATP for the stimulatory site on RyR (Ryanodine Receptor), reducing RyR opening and Ca2+ release.
    • Increased Mg2+ makes it harder for the DHPR (Dihydropyridine Receptor) to open RyR.
    • Decreased ATP (to low levels) decreases RyR opening.

    Lactic Acid and Fatigue

    • The lactate myth began in 1929
    • A relationship between fatigue and lactic acid doesn’t mean that lactate is the cause of the fatigue.
    • Lactate stimulates glucose production in the liver (tissue-to-tissue signaling).
    • Lactate can be used as a fuel by the heart and brain (lactate can be further broken down into pyruvate).
    • Lactate is involved in the release of human growth hormone.
    • Patients with McArdle's disease fatigue quickly, however they lack glycogen phosphorylase meaning that they cannot produce lactate during glycolysis
    • Acidosis decreases the permeability of chloride (Cl-) channels, so the lactate and chloride concentrations in the cell are related.

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    Description

    This quiz covers essential concepts in muscle physiology, including muscle membrane potential ratios and their effects, types of muscle fatigue, and the structure of muscle sarcomeres. It also discusses the impact of eccentric contractions on muscle recovery and function.

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