Neuromuscular Junction: Acetylcholine Release Mechanism

Sequence of Events

1. Action potential arrives at presynaptic terminal
2. Depolarization opens voltage-gated Ca²⁺ channels (P/Q-type)
3. Ca²⁺ influx → binds synaptotagmin on synaptic vesicles
4. Vesicles fuse via SNARE complex (synaptobrevin, syntaxin, SNAP-25) → exocytosis
5. Acetylcholine (ACh) released into synaptic cleft
6. ACh binds nicotinic ACh receptors on motor endplate → Na⁺ influx → endplate potential → muscle AP → contraction

Key Features

• High safety factor (quantal content >> threshold)
• Acetylcholinesterase rapidly hydrolyzes ACh → terminates signal
• Autoimmune (myasthenia gravis) or toxic (botulinum, nerve agents) disruption causes weakness