Physiology

The neuromuscular junction (NMJ) forms a chemical bridge between the motor neurone and skeletal muscle. The final short section of the motor nerve is unmyelinated and comes to lie in a gutter on the surface of the muscle fibre at its mid-point – each being innervated by a single axonal terminal from a fast Aα neurone (en plaque appearance). However, for the intra-occular, intrinsic laryngeal and some facial muscles the pattern of innervation is different with multiple terminals from slower Aγ neurones scattered over the muscle surface (en grappe appearance). Here, muscle contraction depends on a wave of impulses throughout the terminals.

The post-synaptic membrane has many folds; the shoulders contain ACh receptors while the clefts contain the enzyme acetylcholinesterase (AChE), which is responsible for the hydrolysis of ACh (Figure 11.1).

Acetylcholine

Synthesis

The synthesis of ACh (Figure 11.2) is dependent on acetyl-coenzyme A and choline, which is derived from the diet and recycled from the breakdown of ACh. Once synthesized in the axoplasm it is transferred into small synaptic vesicles where it is stored prior to release.

Release

When an action potential arrives at a nerve terminal it triggers Ca2+ influx, which then combines with various proteins to trigger the release of vesicular ACh. About 200 such vesicles (each containing about 10 000 ACh molecules) are released in response to each action potential.

Acetylcholine receptor

Nicotinic ACh receptors are in groups on the edges of the junctional folds on the post-synaptic membrane.