Module 6: Muscle physiology

  • skeletal muscle cells maintain electrochemical gradients and depolarize as a response to neural stimulation

  • depolarization initiates contraction of contraction of muscle through excitation-contraction coupling

neuromuscular junction

  • axon releases ACh

  • nicotinic receptors bind with ACH and Na+ and K+ ion flow which initiates the end of bonding

    • Na+ ion flow causes depolarization

  • End plate potential pushes the voltage gated channels of the motor end plate to threshold, initiation action potential

  • ACh enzyme breaks down ACh and ends excitation


  • triad

  • 1 T-tubule and 2 terminal cisternae of sarcoplasmic reticulum

  • closely associated with area of sarcomere where actin and myosin overlap

  • transverse (T-tubules)-

    • form network within the cell

    • transmit APs deep into the cell

    • lined with DHP receptors which undergo conformational change as a response to AP and is physically attached to RyR

    • RyR- gated Ca2+ channel on terminal cisternae of sarcoplasmic reticulum

    • t-tubules are flanked by terminal cisternae of SR

    • sarcoplasmic reticulum- acts as a Ca++ store until Ca++ ATPase pump returns Ca++ to SR

  • sarcomere- functional unit of myofibril

  • thin filament- composed of actin, troponin, and tropomyosin

    • actin- globular protein with active binding sites for myosin head. 2 chains of actin twisted together to form the main part of the thin filament

    • tropomyosin- regulating protein that blocks myosin binding site on actin at rest

    • troponin- regulating protein with binding sight for Ca2+ and undergoes conformational change to move tropomyosin with Ca2+ is bound

  • actin has a binding site for myosin

  • tropomyosin blocks myosin which has a binding site for Ca2+ which is a binding site for actin at rest

    • undergoes conformational change when bound to Ca++ which moves tropomyosin and exposes myosin binding site on the actin


  • myosin- motor protein of sarcomere that binds and breaks down ATP into ADP and P

    • forms the thick filament

    • isoforms vary between cell types as well as the speed of contraction

  • myosin head- binds ATP, releases actin, repeats steps

    • has binding site for ATP

    • breaks ATP into ADP and P and enters cocked position

      • cocked position has stored energy from ATP and is the myosin’s head usual resting position

    • binds to actin

    • power stroke is when P is released

    • when ADP is released it enters into rigor state

  • titin- elastic protein that connects Z disk to M line and helps align filaments and passively shorten stretched muscle

  • nebulin- inelastic protein associated with thin filaments to help maintain alignment


the motor unit - one motor neuron and the muscle cells it innervates

  • # of myofibers varies in relation to size of muscle, small units with few fibers to large units with thousands of fibers

  • more units are recruited to add more force

    • small units = fine control = small amount of force added

    • large units = efficient force generation = large amount of force added

  • units cycle in and out during longer muscle contractions to avoid fatigue

recruitment

  • number of units recruited = strength of contraction

  • individual units cycle through contraction and relaxation when holding a contraction

    • this avoids overuse and damage of individual units

    • as one relaxes, another takes its place

    • at a constant force, the number of units remain constant while the individual units cycle in and out

fatigue

  • failure to generate or maintain output

  • central-

    • psychological, “all in your head”

    • can choose to continue

    • protects against overuse and injury

  • peripheral-

    • physiological, no choice

    • neuromuscular junction

    • within muscle cell


excitation-contraction coupling process:

1.) ACh from axon terminal binds to nicotinic receptors at the motor end plate which triggers end plate potential

2.) epp pushes the cell to threshold and initiates AP

3.) depolarization occurs in the dihydropyridine receptors (DHP) that are on the t-tubules

4.) DHP undergoes conformational change and opens ryanodine receptors (RyR) on the sarcoplasmic reticulum and Ca++ is released

5.) Ca++ diffuses and binds to troponin

  • tropomin triggers a conformational change that moves the tropomyosin which exposes the binding site on the actin filament

6.) myosin head binds to actin as a crossbridge formation

7.) myosin performs a power stroke, shortening the sarcomere

8.) sarcolemma repolarizes which reaches the DHP receptors which causes conformational change back to resting state which closes the RyR preventing Ca++ to be released from the SR

9.) Ca++ -ATPase pump moves Ca++ back into the SR which causes the concenration of Ca++ to drop in sarcoplasm

10.) Ca++ is released from troponin, triggering conformational change that moves the tropomyosin back over the myosin binding site that blocks the cross-bridge formation and makes the myofiber relax