Somatic Neuromuscular Transmission

The presynaptic nerve terminal is the site of synthesis, release, and reuptake of the neurotransmitter acetylcholine (ACh), the chemical responsible for neuromuscular transmission. Acetylcholine is synthesized in the peripheral nerve terminal when acetate derived from acetyl CoA within the mitochondria and choline that has been recycled and taken up from the synaptic cleft is catalyzed by the enzyme choline acetyltransferase. The newly formed acetylcholine is then packaged into synaptic vesicles within the nerve terminal. Some ACh vesicles are located immediately adjacent to the nerve terminal membrane and are available for immediate release, whereas others are localized a short distance from the terminal nerve membrane and mobilized for rapid release.

ACh release is triggered by calcium influx into the nerve terminal. As a propagating nerve action potential reaches the nerve terminal, the depolarization activates voltage-gated calcium channels in the active zones of the terminal membrane, resulting in an influx of calcium (Ca²⁺) ions into the axon terminal. The Ca²⁺ binds to active zones within the nerve terminal lying in juxtaposition to the muscle postsynaptic ACh receptors. This allows for synaptic vesicle membrane fusion to the nerve terminal membrane, with ACh release into the synaptic cleft.

The synaptic cleft is the neuromuscular junction site where ACh released from the nerve terminal crosses and eventually binds to postsynaptic muscle membrane ACh receptors. The time required for ACh to move across the synaptic cleft is slower than electrical impulse transmission along the axon or muscle fiber membrane. Unlike action potential transmission, movement of ACh across the cleft is unidirectional. ACh remaining within the cleft, either before or after attachment to the ACh receptors, is rapidly degraded within the synaptic cleft into acetate and choline by acetylcholinesterase (AChE), thus terminating its activity. Subsequently, choline is redirected into the nerve terminal and recycled to form new ACh transmitters.

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