Lab 5: Muscle Physiology

• Neuromuscular junction
  • Axon terminal releases ACh
  • Motor end plate lined with nicotinic receptors
  • ACh binds to nicotinic receptors, ion flow (Na+ and K+) initiates end-plate potential (EPP) → action potential
  • AChE (acetylcholinesterase) breaks down ACh, ending excitation at motor end plate
• Triad – one t-tubule and 2 flanking terminal cisternae of sarcoplasmic reticulum, closely associated with area of sarcomere where actin and myosin overlap
  • Transverse tubules (t-tubule) – invagination of sarcolemma
  • Form network within cell, allows action potential to travel deep, lined with DHP receptors
  • DHP receptor (dihydropyridine)- undergoes conformational change in response to action potential, physically attached to RyR
  • RyR (ryanodine receptor) – gated Ca++ channel on terminal cisternae of sarcoplasmic reticulum
  • Sarcoplasmic Reticulum – acts as Ca++ store, Ca++ sequestered inside at rest, Ca++ ATP-ase pump returns Ca++ to SR
• Sarcomere – functional unit of myofibril
  • Thin filament – composed of actin, troponin and tropomyosin
  • Actin – globular protein with active binding site for myosin head, two chains of actin twisted together form main part of thin filament
  • Tropomyosin – regulatory protein that blocks myosin binding site on actin at rest
  • Troponin – regulatory protein with binding site for Ca++, undergoes conformational change to move tropomyosin when Ca++ is bound
  • Myosin – motor protein of sarcomere that binds and breaks down ATP → ADP + Pi
  • Forms thick filament
  • Isoform varies between muscle cell types, speed of contraction varies among isoforms
  • Myosin head
    • Binding and breakdown of ATP puts it into cocked position, ready to bind to actin, ADP and Pi remain bound (usual resting state)
    • Binds to actin when active site is available
    • Pi is released and power stroke occurs
    • ADP is released but head still bound to actin (rigor state)
    • ATP must be bind again to release and restart cycle
  • Titin – elastic protein connecting Z disk to M line, helps align filaments and passively shorten stretched muscle
  • Nebulin – inelastic protein associated with thin filament, helps maintain alignment
• Excitation-contraction coupling
  • EPP → AP → DHP receptor conformational change → RyR opening allowing Ca++ into sarcoplasm as secondary messenger → Ca++ binds to troponin → troponin moves tropomyosin, exposing myosin binding site on actin → myosin binds actin, performs power stroke
  • EMG detects AP along sarcolemma
• Motor Unit – one motor neuron and the muscle cells it innervates
  • Number of myofibers varies in general relation to size of muscle, small units with few fibers to large units with thousands
  • More units recruited to add more force
  • Few units = small amount of force added = fine control
  • Large units = large amount of force added = more efficient force generation
  • Units cycle in and out during longer muscle contractions to avoid fatigue
• Fatigue – failure to generate or maintain output
  • Central – psychological, can chose to continue
  • Peripheral – physiological failure, no choice

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