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