Neuromuscular Junction - Mechanism of Action

Mechanism of Action

The neuromuscular junction is the location where the neuron activates muscle to contract. This is a step in the excitation-contraction coupling of vertebrate skeletal muscle.

1. Upon the arrival of an action potential at the presynaptic neuron terminal, voltage-dependent calcium channels open and Ca2+ ions flow from the extracellular fluid into the presynaptic neuron's cytosol.
2. This influx of Ca2+ causes neurotransmitter-containing vesicles to dock and fuse to the presynaptic neuron's cell membrane through SNARE proteins.
3. Fusion of the vesicular membrane with the presynaptic cell membrane results in the emptying of the vesicle's contents (acetylcholine) into the synaptic cleft, a process known as exocytosis.
4. Acetylcholine diffuses into the synaptic cleft and binds to the nicotinic acetylcholine receptors bound to the motor end plate.
5. These receptors are ligand-gated ion channels, and when they bind acetylcholine, they open, allowing sodium ions to flow in and potassium ions to flow out of the muscle's cytosol.
6. Because of the differences in electrochemical gradients across the plasma membrane, more sodium moves in than potassium out, producing a local depolarization of the motor end plate known as an end-plate potential (EPP).
7. This depolarization spreads across the surface of the muscle fiber and continues the excitation-contraction coupling to contract the muscle.
8. The action of acetylcholine is terminated when the enzyme acetylcholinesterase degrades part of the neurotransmitter (producing choline and an acetate group) and the rest of it diffuses away.
9. The choline produced by the action of acetylcholinesterase is recycled — it is transported, through reuptake, back into the presynaptic terminal, where it is used to synthesize new acetylcholine molecules.