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