Muscle Physiology Notes

Muscle Physiology Learning Objectives

  • Define sarcomere, actin, myosin, tropomyosin, troponin, sarcolemma, t-tubules, sarcoplasmic reticulum, dihydropyridine receptor (DHPR), ryanodine receptor (RyR), twitch fibers, ATP
  • Describe how the structures of muscle fibers allow for the function of muscle tissue.
  • Assess metabolic pathways for generation of energy for muscle movements.
  • Compare isometric, concentric, and isotonic skeletal muscle contractions.
  • Describe the sliding filament theory of muscle contraction, including the sequence of molecular interactions leading to contraction.
  • Explain how excitation and contraction of myocytes are coupled, beginning with motor neuron stimulation.
  • Determine the work relationship between whole muscle contractions, contractile force and tension.

Muscle Tissue

  • Muscle is a tissue built of specialized contractile cells (called myocytes or muscle fiber).
  • There are two main categories of muscle:
    • Striated muscle tissue
      • Has the appearance of alternating light and dark bands, which are collections of contractile proteins called myosin and actin arranged into repeating units (sarcomeres)
      • With vertebrates – striated muscle are:
        • Skeletal muscle – locomotion and posture
        • Cardiac muscle – pump blood/lymph through heart
    • Smooth muscle tissue
      • Also uses contractile proteins actin and myosin, but they are not organized into sarcomeres
      • In vertebrates - smooth muscle lines hallow and tubular organs

Smooth Muscle

  • In vertebrates:
    • Locations:
      • Gastrointestinal tract
      • Respiratory tract
      • Reproductive tract
      • Urinary tract
      • Eyes
      • Base of hairs or feathers
    • Functions for hollow organs:
      • Changing size and volume
        • Example: uterus and bladder
      • Propelling material along a tube
        • Example: partially digested food thru small intestines
      • Maintaining tension for long periods of time
        • Example: sphincters of the bladder or anus

Cardiac Muscle

  • Only muscle that makes up the heart
  • Like skeletal muscle:
    • Has striations with actin and myosin arranged in sarcomeres
    • Have a single nucleus
  • Uniqueness:
    • Adjacent heart myocytes connected by intercalated discs containing gap junctions
    • Gap junctions – allow for ions to pass quickly from 1 myocyte to the next
    • Electric coupling ensures all cells connected by these gap junctions will contract at the same time
    • Specialized pacemaker cells – maintain the rhythm for the contractile activity of the heart

Skeletal Muscle Fibers (Muscle Cells) Structure

  • Multinucleated cells that originate from myoblasts
  • Surrounded by a sarcolemma (plasma membrane)
  • Muscle fibers contain 100s of myofibrils
  • Repeating bands: dark A bands and lighter I bands
  • Contracting unit of muscle fibers is the sarcomere

Skeletal Muscle Fibers (Muscle Cells)

  • Muscle fibers contain myofibrils > sarcomeres > myofilaments
  • There are two kinds of myofilaments:
    • Thin filaments made mostly from actin proteins with regulatory proteins troponin (TN) and tropomyosin (TM)
    • Anchored to Z discs by nebulin protein
    • Actin extends from Z discs partway into the A band
    • TN and TM control access of actin from the myosin cross-bridges
    • Thick filaments are made of myosin proteins
    • Contain crossbridges or myosin heads with binding sites for actin and ATP
    • Titan protein maintains thick filaments at the center of the sarcomere

Skeletal Muscle Contractions

  • Cross-bridges of the thick filaments draw the thin filaments toward the center of each sarcomere.
  • Muscle contractions require myosin filaments to pull actin filaments inward, thereby shortening the muscle fiber
  • Requirements:
    • Ca^{2+} binding to troponin >> troponin pulls tropomyosin out of the way and exposes actin binding sites to myosin head (cross-bridge)
    • Ca^{2+} necessary to expose actin binding sites to myosin
    • ATP binding necessary for detachment of myosin from actin
    • ATP hydrolysis to ADP and Pi provides energy for power stroke

Skeletal Muscle Contractions - Key Points

  1. Before ATP binding, myosin and actin are in the rigor conformation state
  2. ATP binding allows myosin head to release actin
  3. Once ATP hydrolysis occurs, myosin-ADP-Pi requires Ca^{2+} to have exposed the actin binding sites for the myosin heads
  4. Release of Pi allows the chemical energy to drive the power stroke
  5. ADP release returns the rigor conformation

Smooth Muscle Contractions

  • Smooth muscle actin and myosin filaments are arranged around the cells’ periphery
  • Structure of myofilaments:
    • Greater proportion of actin to myosin with actin filaments attached to dense bodies
    • Thick filaments have cross-bridges (myosin heads) along the entire length
  • Contractions:
    • Cross-bridge actions cause cell to shorten and plum in the center
    • Smooth muscle myosin ATPase occurs at a slower rate compared to skeletal muscle myosin ATPase.
      • Results in:
        • Slower speed of contraction
        • Longer contraction time

Cellular Protein Role in Animal Physiology

  • Membrane proteins can also be ligand-gated
  • Some cone snail toxins specifically target these ligand-gated channels

Skeletal Muscle Contractions Are Voluntary

  • Depend on neural excitation
  • Each muscle fiber is innervated by a motor neuron
  • Motor neurons release a chemical neurotransmitter called acetylcholine into the neuromuscular junction between the motor neuron and the muscle fiber’s sarcolemma
  • Influx of positively charged Na^+ ions thru the ligand gated channels depolarizes the sarcolemma = excitation
  • Excitation leads to activation of the contractile machinery with release of Ca^{2+} and a subsequent contraction.

Skeletal Muscle Fibers (Muscle Cells) Structure

  • Multinucleated cells that originate from myoblasts
  • Surrounded by a sarcolemma (plasma membrane)
  • Transverse tubules are continuous with the sarcolemma and transverse the long axis of the muscle fiber
  • T-tubules are closely associated with the sarcoplasmic reticulum that envelops myofibrils and contain high amounts of Ca^{2+}
  • Ca^{2+} release from the sarcoplasmic reticulum depends on two proteins: DHPR and RyR calcium channels
  • T-tubules have dihydropyridine receptors (DHPR) that are voltage-gated and change conformation when the t-tubule membrane depolarizes
  • The sarcoplasmic reticulum has ryanodine receptors (RyR) that touch DHPR and open

Skeletal Muscle Contractions Are Voluntary (DHPR and RyR)

  • Before t-tubules’ dihydropyridine voltage-gated receptors (DHPR) are stimulated: Muscle cell at rest: rigor conformation = calcium
  • After t-tubules’ dihydropyridine voltage-gated receptors (DHPR) are stimulated: Muscle cell with exposed actin biding sites for myosin head cross-bridges = calcium
  • After depolarization is over (motor neuron is no longer releasing acetylcholine to stimulate the ligand- gated channels):
    • DHPR and RyR reclose
    • ATP-dependent Ca^{2+} pumps decrease cytosol calcium levels. Muscle cell returning to rest and rigor conformation = calcium

Muscle Energetics

  • Vertebrate muscles have 3 sources for ATP:
    1. Phosphagen creatine phosphate
    2. Anaerobic glycolysis
    3. Aerobic catabolism
  • Phosphagen creatine phosphate – rapid production, short lived (~10 seconds)
  • Anaerobic glycolysis – moderate production; will eventually be exhausted with a state of all-out-exertion
  • Aerobic catabolism – lowest rate of production; can be maintained on a relatively sustained basis
  • Vertebrate muscles fibers can be grouped based upon:
    • Myosin ATPase activity
    • Metabolic feature after creatine phosphate is used up
      1. Slow oxidative (SO) fibers - Type I
        • Rich in myoglobin and mitochondria, appear red, and slow to fatigue
        • Slow ATPase activity
        • Make ATP principally by oxidative phosphorylation
      2. Fast glycolytic (FG) fibers - Type II
        • Little myoglobin, rich in glycogen, appear white, fatigue quickly
        • Fast ATPase activity
        • Make ATP principally by anaerobic glycolysis
      3. Fast oxidative glycolytic (FOG) fibers - Type II
        • Rich in mitochondria and myoglobin, intermediate resistance to fatigue
        • Predominantly use oxidative phosphorylation to make ATP

Whole Skeletal Muscle

  • Skeletal muscle is made up of 100s of muscle fibers that work in concert for coordinated movements
  • Connective tissues surround the individual fibers and organize them into functional bundles
  • The connective tissue is continuous with tendons that connect muscles to bones
  • The organization of the sarcomeres results in pulling motions only
  • Whole muscles work in antagonist pairs to pull opposite sides of skeletal joints
    • Gastrocnemius (calf muscle) pulls on the heel bone to extend the foot downward
    • Shortening of the cranial tibial muscle allows for flexing of the foot upward and re-lengthening the calf muscle.

Muscle Contraction – Force Generated by Cross Bridge Activity

  • Isometric contraction
    • Sarcomere may shorten slightly but maintains tension
    • Whole muscle stays the same length
    • Purpose: help animals hold a steady, unmoving posture
    • Ex: a stalking cat that is poised midstep
    • Ex: tightening the bicep muscle without allowing your elbow joint to move
  • Muscles exert its force on a load where the force of the muscle opposes the force of the load
  • Concentric contraction
    • Force is generated, whole muscle shortens
    • Ex: tightening the bicep muscle to pick up a weight thereby reducing the angle of the elbow joint
    • Maximum tension developed when muscle fibers have the optimal overlap of thin filaments with myosin cross-bridges
  • Eccentric contraction
    • Force is generated where the whole muscle lengthens
    • The contractile activity is resisting stretch imposed by external forces
    • Ex: Slowly lengthening a tightened bicep (with the triceps being the antagonists) to lower a weight down and extend the elbow joint
    • NOTE: eccentric contractions and the damage caused with the cellular processes needed to repair the damage is primarily responsible for delayed muscle soreness

Muscle Contraction - Overall Work Performed

  • Muscles do work when they change the position of objects with mass
  • Amount of work = force x distance
  • Work = Force * Distance
  • Gives insight into the amount of energy that is transferred from muscle to the load
  • Muscles will consume energy as they produce force, even if they are not moving a load
  • Greatest amount of work will be performed when the sarcomeres are at their optimal length prior to contracting
  • If a muscle contracts and no load is present, no work is done
  • If the force to move an object is greater than the muscle can perform, the distance = 0 and no mechanical work occurs
  • Example: Tetanus (an acute, infectious disease caused by spores of the bacterium Clostridium tetani)
    • Tetanus toxin prevents inhibition of motor neurons firing so the motor neurons continue to fire and cause the muscles to sustain a contraction