Acetylcholine

Acetylcholine, abbreviated ACh, is a small-molecule neurotransmitter used for chemical signaling in both the central and peripheral nervous systems. It is especially important at the neuromuscular junction, where motor neurons release acetylcholine to activate skeletal muscle fibers, and in the autonomic nervous system, where it transmits signals at autonomic ganglia and from most parasympathetic postganglionic neurons to their target tissues .^1,2

Acetylcholine is synthesized inside nerve terminals from choline and acetyl coenzyme A by the enzyme choline acetyltransferase. It is then stored in synaptic vesicles. When an action potential reaches a cholinergic nerve terminal, calcium-dependent vesicle fusion releases acetylcholine into the synaptic cleft, where it binds to receptors on nearby cells .^1,2

Acetylcholine acts through two major receptor families. Nicotinic acetylcholine receptors are ligand-gated ion channels that produce relatively rapid electrical responses and are found, for example, at skeletal neuromuscular junctions and autonomic ganglia. Muscarinic acetylcholine receptors are G protein-coupled receptors that produce slower and more varied cellular responses. Because different receptor subtypes activate different signaling mechanisms, acetylcholine can have different effects depending on the tissue and receptor involved .^1,2

Acetylcholine signaling is usually brief because the enzyme acetylcholinesterase rapidly breaks down acetylcholine into choline and acetate after its release. Choline can then be taken back into cholinergic nerve terminals and reused for acetylcholine synthesis .^1,2