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Physiology of neuromuscular transmission.
Every propagated nerve action potential along the motor axon results in a propagated muscle action potential under normal conditions. Communication between nerve and muscle occurs via transfer of acetylcholine (ACh) molecules across the neuromuscular junction. In this region, both motor nerve terminals and muscle membranes are specialized for this unique function. The motor nerve terminal contains membrane-enclosed vesicles containing ACh (formed from choline and acetyl coenzyme A by choline acetyl transferase). The ACh vesicles are found in two forms, those ready for immediate release and those that are stored but can be transferred for immediate release. Those ready for immediate release (1,000-2,000 per terminal) are lined up along dense bars within active zones. Active zones are specialized regions of the motor nerve terminal that oppose specialized regions of the postsynaptic muscle membrane, the primary junctional folds. The primary junction folds contain acetylcholine receptors (AChR) in high density. Therefore, when the vesicles line up along the active zone and are released by the depolarized motor nerve, the released ACh-containing vesicles have a greater chance of combining with an available receptor. [1]
The number of ACh-containing vesicles released by the presynaptic neuron is dependent on the existing number of vesicles ready for immediate release before depolarization, the concentration of calcium in the extra- and intracellular milieu, and the amplitude and duration of the presynaptic membrane depolarization. When the presynaptic membrane is depolarized, calcium enters the cell and activates the intracellular protein calmodulin. Activated calmodulin binds with a protein receptor next to the active zone, allowing movement of the vesicles toward the active zone. The number of vesicles released far exceeds the number needed to activate a propagated action potential in the muscle cell membrane (safety factor).
The joining of ACh molecules to the AChR causes a voltage-gated sodium channel in the muscle …
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