Muscular contraction?

Question

What are the sequence of molecular events that produces force and shortening in muscle, starting from the arrival of the action potential at the neuromuscular junction, and ending with the release of phosphate from myosin?

Answer 1

When the action potential (AP) arrives in the nerve terminal, it depolarizes it, which causes the opening of voltage-gated calcium channels. Calcium diffuses into the neuron and promotes the binding of synaptic vesicles to the neuron terminal membrane. Exocytosis releases acetylcholine into the synaptic cleft. It diffuses across, and binds to nicotinic receptors at the end-plate of the muscle. This binding opens a channel, and enough sodium flows into the muscle cell to depolarize it, causing an AP in the muscle in turn. The AP flows along the muscle cell membrane, including down the transverse (t-) tubules. In the t-tubules are dihydropyridine receptors. Depolarization causes these receptors to trigger ryanodine receptors in the sarcoplasmic reticumul (SR) membrane inside the muscle cell. This opens calcium channels in the SR, and allows the calcium (which is stored in the SR) to flow into the myoplasm. The calcium binds to troponin on the actin. This binding "unlocks" the troponin, which in turn allows the tropomyosin to move away from the myosin-binding site on the actin. With the binding site open, the actin and myosin can interact. The myosin is already in the energized state because ATP had bound to it previously; the ATP is broken down into ADP and inorganic phosphate and the energy is used to change the angle of the myosin head so it can interact with the actin. (Which it could not do previously because the myosin-binding site on the actin was covered by the tropomyosin). The binding of the actin and myosin to each other change the conformation of the myosin head group slightly, so the inorganic phosphate is released. This allows the "power stroke" so the myosin attached to the actin, moves towards the center of the sarcomere, thus shortening the muscle and returning the myosin to the unenergized state.