Events at the Neuromuscular Junction:

I. Nerve impulses (action potentials) travel from brain or spinal cord to trigger action of skeletal muscles
A. Action potential propagates down motor neuron to skeletal fiber
1. Site where excitation happens is neuromuscular junction
a) This junction is chemical synapse consisting of points of contact between axon terminals of motor neuron and motor end plate
of skeletal muscle fiber
II. 7 Steps
A. 1) Action potential travels length of axon to axon terminal
B. 2) voltage-gated calcium channels open and calcium ions diffuse into terminal
C. 3) Calcium entry causes synaptic vesicles to release Acetylcholine (Ach) via exocytosis
D. 4) Ach diffuses across synaptic cleft and binds to Ach receptors which contain ligand-gated cation channels
E. 5) Ligand-gated channels open
F. 6) Na ions enter muscle fiber and K exit
1. Greater flux of Na ions relative to outward flux of K ions causes membrane potential to become less negative
G. 7) Once membrane potential reaches a threshold value, an action potential propagates across sarcolemma
1. Neural transmission ceases when Ach is removed from synaptic cleft, occurs in two ways
a) 1) Ach diffuses away
b) 2) Ach is broken down Acetlycholinesterase into choline and Acetic acid
(1) Choline is transferred into terminal for resynthesis of Ach

Excitation-Contraction Coupling
I. Typically, a single motor neuron, arising in brain or spinal cord, conducts action potential that travels to hundreds of skeletal fibers within a
muscle
II. Sequence of events that converts action potential, in a muscle fiber, to a contraction is known Excitation-Contraction Coupling
III. In single muscle fiber, action potential travels through entire sarcolemma and is rapidly conducted into interior of muscle fiber by
transverse tubules (T tubules)
A. T tubules are regularly spaced infolding of sarcolemma that branch extensively throughout muscle fiber
1. At numerous junctions, T tubules make contact with sarcoplasmic reticulum (SR)—which is calcium-storing membranous
network
2. Where SR directly touches T tubule—> SR forms sac-like bulges called Terminal cisternae (on either side) and the T tubule plus
two, adjacent on either side, terminal cisternae is known as a Triad
3. Membranes of T tubule and terminal cisternae are linked by series of proteins that control calcium release.
a) As action potential travels down T tubules, causes voltage-sensitive protein to change shape
(1) This opens calcium-release channel in SR which allows calcium ions to flood sarcoplasm—fluid area (cytoplasm) around
SR and T tubules
b) Rapid influx of calcium triggers contraction of skeletal muscle fiber
(1) thus, calcium ions are responsible for coupling of excitation and contraction of skeletal muscle fibers

The Cross Bridge Cycle

I. Contraction of skeletal muscle generates force to move muscle
A. Contraction triggered by series of events known as cross bridge cycle
II. Functional unit of contraction is Sarcomere
A. Sarcomere shortens when myosin heads and thick myofilaments form cross bridges with actin molecules and think myofilaments
III. Formation of cross bridge
A. Initiated when Calcium ions (released from SR) bind to troponin
1. Binding causes troponin to change shape
B. Tropomyosin moves away from myosin-binding sites allows myosin head to bind to actin and form cross bridge
C. Myosin head must be activated as well
1. Occurs when ATP binds to myosin head and is hydrolyzed to ADP and inorganic phosphate
a) Energy from hydrolysis activates myosin head and forces it into cocked position
IV. Cross bridge cycle has 4 Steps
A. 1) Cross bridge formation
1. Activated myosin head binds to myosin to form cross bridge
a) Inorganic phosphate released and bind, between myosin and myosin-binding site aka actin, becomes stronger
B. 2) Power Stroke
1. ADP is released and activated myosin head pivots, sliding thin myofilament towards center of Sarcomere
C. 3) Cross bridge detachment
1. When another ATP binds to myosin, link between myosin and actin becomes weaker and detaches
D. 4) Reactivation of myosin head
1. ATP is hydrolyzed to ADP and inorganic phosphate; energy release puts myosin head into cocked position again
a) As long as binding sites on actin remain exposed, cross bridge cycle will repeat
(1) As cycle repeats, thin myofilaments and pulled toward each other and sarcomere shortens
(a) Shortening causes whole muscle to contract
V. Cross bridge ending
A. When Calcium ions are actively transported back into SR
B. Troponin returns to original shape allowing tropomyosin to cover myosin-binding site on actin