muscle physiology

• Skeletal muscle fiber


  • 3-4 in. in length
  • 0.05-0.15 mm wide
  • Each fasciculus holds 100-150 fibers
  • Contain hundreds to thousands of nuclei
  • Develop through fusion of mesodermal cells (myoblasts)

  
• Sarcolemma


  Cell membrane (specific to muscle) that surrounds the sarcoplasm
• Transverse tubules (T tubules)


  Transmit action potential through cell, allow entire muscle fiber to contract simultaneously, have same properties as sarcolemma

  
• Myofibrils


  • Made up of bundles of protein filaments
  • responsible for muscle contraction
  • Give skeletal and cardiac muscle striated appearance
  • Orderly arrangement of thick and thin filaments
• Sarcoplasmic reticulum (SR)


  Membranous structure surrounding each myofibril, helps transmit action potential to myofibril, forms chambers (terminal cisternae) attached to T tubules
• Triad


  1 T tubule and 2 terminal cisternae, cisternae concentrate Ca2+ and release Ca2+ into sarcomeres to begin muscle contraction
• Actin


  Contractile protein, each G actin has a binding site for myosin, filamentous actin composed of 2 rows of 300-400 G-actin molecules in a twisted strand arrangement, G-actin has active sites that can bind with myosin
• Tropomyosin


  Regulatory protein that overlaps binding sites on actin for myosin
• Troponin


  Regulatory protein complex of 3 proteins: 1) attaches to actin, 2) attaches to tropomyosin, 3) binds Ca2+ reversibly, Ca2+ binding regulates skeletal muscle contraction
• Myosin


  Thick myofilament, myosin tail is toward the M line, myosin head is toward the I band, myosin head has actin binding site and nucleotide binding site for ATP and ATPase
• Titin


  Strands of elastic protein that extend from Z-disk to next M-line, huge elastic molecule (~25,000 AA), stabilizes position of contractile filaments, returns stretched muscle to rest
• Sliding filament model


  Muscle contraction shortens sarcomere as thick and thin filaments slide past each other, A band stays same length, I band and H zone shorten
• The sliding filament model and crossbridge cycle explain how muscles generate force
• Crossbridge cycle


  • ATP is hydrolyzed
  • Unbinding of myosin and actin
  • Cocking of the myosin head (myosin in high-energy form)
  • Binding of myosin to actin
  • Inorganic phosphate is released
  • Power stroke
  • Rigor (myosin in low-energy form)
  • New ATP binds to myosin head
  • ADP is released
• Excitation-contraction coupling


  1. Action potential in sarcolemma

  2. Action potential down T tubules

  3. DHP receptors of T tubules open Ca2+ channels (ryanodine receptors) in lateral sacs of SR

  4. Ca2+ increases in cytosol

  5. Ca2+ binds to troponin, shifting tropomyosin

  6. Crossbridge cycling occurs
• Neuromuscular junction


  • Acetylcholine (ACh) is released from the axon terminal of a motor neuron and binds to receptors in the motor end plate
  • This binding elicits an end-plate potential, which triggers an action potential in the muscle cell
• Troponin and tropomyosin


  • If no Ca2+ → troponin holds tropomyosin over myosin binding sites on actin, no crossbridges form, muscle relaxed
  • If Ca2+ present → binds to troponin, causing movement of troponin, causing movement of tropomyosin, exposing binding sites for myosin on actin, crossbridges form, muscle contracts
• How a contraction stops


  1. APs must stop

  2. ACh-esterase degrades ACh

  3. T-tubule voltage-gated Ca2+ channels close

  4. Ca2+ must be removed from cytoplasm

  5. SR Ca2+ ATPase removes Ca2+ from sarcoplasm
• Role of ATP in contraction/relaxation


  • ATP needed for cross bridge formation
  • ATP needed for unbinding of actin and myosin
  • ATP needed for Ca2+ pump – back into SR
• Rigor mortis


  • State of muscular rigidity
  • Begins 2-3 hours after death
  • Lasts about 24 hours
  • After death, Ca2+ ions leak out of the SR and allow myosin heads to bind to actin
  • Ion pumps cease to function (no ATP)
  • As ATP synthesis has ceased, crossbridges cannot detach from actin
  • Need proteolytic enzymes to begin digesting decomposing cells
• Muscle twitch


  • Single contraction-relaxation cycle
  • Response to a single electrical stimulus
  • All-or-none principle
  • Latent period - time required for Ca2+ to bind to troponin
  • Contraction phase - muscle tension increases to a maximum
  • Relaxation phase - tension then decreases
• Isometric and isotonic twitches


  • Contractile elements = sarcomeres
  • Series elastic elements = connective tissue, tendons
  • Force exerted by contracting muscle = tension
  • Force opposing contraction (such as weight to be moved) = load
• Isometric contraction


  • Length constant, contractile elements contract, generating tension, when load > tension, stretches series of elastic elements, muscle does not shorten, load not lifted
  • Isometric contraction continues (tension increases) until tension exceeds load, then isotonic contraction begins
• Isotonic contraction


  Constant tension, when tension > load, load is lifted as muscle shortens, if muscle tension > load (resistance), muscle shortens (concentric contraction)
• • Normal muscle activity involves both isometric and isotonic contractions, even if the load is constant, isometric precedes isotonic phase of contraction
  • Load generally not constant, load changes as limb position changes
• Motor unit (MU)


  • Motor neuron (MN) and all muscle fibres it innervates, activate MN and all muscle fibres in MU contract
  • Number of muscle fibres in MU varies according to degree of fine control capability of the muscle
  • Innervation ratio (# MN : muscle fibres) varies from 1:few to 1:2000
  • Ratio varies within a muscle
• Innervation ratios in different muscles


  • Gastrocnemius ~2000 fibres/MU
  • Extraocular 3-5 fibres/MU
• Slow twitch (type I) muscle fibres


  Fatigue resistant, lower force/power
• Fast twitch (type II) muscle fibres


  Powerful, fatigable
• Intermediate (type IIA) muscle fibres


  More fatigue resistant than IIX but less than I, intermediate force/power
• Tension production in whole muscle


  1. MU activation (frequency of MU activation, temporal summation)

  2. Number of MUs recruited (spatial summation, sustained tension, less than maximal tension, allows MUs rest in rotation)
• Twitch summation


  If time between action potentials is too slow, complete recovery, if shortened, temporal summation (more forceful contraction)
• Incomplete or unfused tetanus


  Stimulation frequency is too low, muscle fibre not firing at max value
• Complete tetanus


  If stimulation frequency is high enough, muscle never begins to relax, continuous contraction, maximal force development
• Increase in tension development in single muscle fibre by increasing rate of action potentials
• Resting fibre length


  Twitch force depends on length of individual sarcomeres before contraction, optimal overlap of thin and thick filaments, tension a muscle fibre can generate is directly proportional to the number of crossbridges formed between thick and thin filaments
• Resting length of muscle


  Tension (% of maximum)
• Motor unit sizes


  Number of motor units varies in different muscles, size of motor units varies, small for delicate movements, large for strength movements, fiber diameter (and thus strength) varies in motor unit
• The size principle


  Order of motor unit recruitment is related to size of motor units, small units recruited first, large units recruited last, larger neurons are more difficult to depolarize to threshold, requires greater synaptic input
• Asynchronous recruitment of motor units helps prevent fatigue (submaximal)