Acetylcholine: the neurotransmitter of movement, autonomic function, and cognition

Biology and chemistry

Acetylcholine is synthesized from choline and acetyl-CoA by the enzyme choline acetyltransferase. Once released into a synapse, it acts on two major receptor families and is rapidly broken down by acetylcholinesterase into choline and acetate; choline is taken back up into the presynaptic cell for reuse. More on synthesis and breakdown is available at this resource.

Receptors and actions

• Nicotinic receptors — ion-channel receptors found at the neuromuscular junction and on many autonomic ganglia; they mediate fast synaptic transmission.
• Muscarinic receptors — G-protein coupled receptors prominent in the heart, smooth muscle, glands, and many brain regions; they produce slower modulatory effects.

Differences between these receptor types help explain why acetylcholine can produce both rapid and prolonged effects in different tissues. See more on receptor types.

History and discovery

The role of acetylcholine as a chemical messenger emerged in the early 20th century through experiments that showed chemical transmission between nerves and target tissues. Key figures in this work include researchers who demonstrated that nerves could release a substance that mimicked stimulation of the vagus nerve. A historical overview is found at additional history.

Clinical relevance and examples

Alterations of cholinergic signaling are implicated in several medical conditions and are targets for therapy. Loss of cholinergic neurons in parts of the brain is associated with cognitive decline and dementia; cholinesterase inhibitors are used to enhance acetylcholine levels in such disorders. Substances that affect acetylcholine include nicotine (agonist), curare (nicotinic antagonist), botulinum toxin (prevents release), and organophosphate pesticides or nerve agents (acetylcholinesterase inhibitors). For clinical details, consult further reading.

Overall, acetylcholine is a versatile and ubiquitous neurotransmitter whose synthesis, receptors, and regulation underpin essential functions from voluntary movement to autonomic control and higher cognitive processes.