acetylcholines

Acetylcholine, sometimes encountered as acetylcholines, is a neurotransmitter in both the peripheral and central nervous systems. It is an ester formed from acetic acid and choline, produced in cholinergic neurons by the enzyme choline acetyltransferase, which uses acetyl-CoA as the acetyl donor. The neurotransmitter is stored in synaptic vesicles and released into the synaptic cleft in response to an action potential.

On binding, acetylcholine activates two major receptor families: nicotinic acetylcholine receptors (nAChRs), ligand-gated ion channels that mediate fast synaptic transmission, and muscarinic acetylcholine receptors (mAChRs), G protein–coupled receptors with diverse physiological effects. In the neuromuscular junction, nAChR activation triggers muscle contraction; in the autonomic nervous system, acetylcholine modulates heart rate, glandular secretion, and smooth muscle. In the brain, acetylcholine modulates attention, learning, and memory, among other functions.

Termination of signaling occurs rapidly through hydrolysis by acetylcholinesterase into choline and acetate. Choline is taken back up into the presynaptic neuron via a high-affinity choline transporter and reused to synthesize new acetylcholine.

Clinical relevance: deficits in cholinergic signaling are linked to cognitive decline in Alzheimer's disease; acetylcholinesterase inhibitors are used to treat symptoms by increasing acetylcholine levels. Excess acetylcholine action, such as from organophosphate poisoning, causes cholinergic toxicity. Botulinum toxin impairs acetylcholine release, producing flaccid paralysis.