The translation of an action potential in the motor nerve to muscle contraction begins at the neuromuscular junction ( Fig 3). Depolarization opens voltage-gated Ca2+
channels concentrated in the nerve terminal membrane (Fig, 4) (Ke®.sey!989). Ca2+ influx promotes the mobilization and fusion of preformed vesicles containing acetylcholine with active zone particles on the intracellular surface of the nerve terminal, and the exocytosis of their contents. Voltage-gated Ca 2+ channels are blocked by high concentrations of extracellular magnesium, explaining the neuromuscular blockade seen in hypermagnesemia. In the Lambert-Eaton myasthenic syndrome, antibodies directed against voltage-gated Ca2+ channels prevent Ca2+ influx and therefore decrease acetylcholine release in response to depolarization
Fig. 4 The neuromuscular junction. The nerve terminal, synaptic cleft, and muscle endplate are shown: ACh, acetycholine; AChE, acetylcholinesterase; VGCC, voltage-gated Ca2+ channels; AChR, acetylcholine receptors.
After release, acetylcholine crosses the synaptic cleft and interacts with acetylcholine receptors on the crests of muscle postsynaptic junctional folds ( Fig 4). The opening of acetylcholine receptors allows the movement of Na+ into the muscle fiber and the generation of an excitatory endplate potential. When of sufficient amplitude, nearby voltage-gated Na+ channels are opened and an action potential is generated. Acetylcholine is hydrolyzed by acetylcholinesterase, terminating its action. In myasthenia gravis, anti-acetylcholine receptor antibodies interfere with neuromuscular transmission, resulting in muscle weakness ( Ke§sey!98.9.).
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