Nicotinic Acetylcholine Receptor

A nicotinic acetylcholine receptor, or nAChR, is a membrane protein that acts as both a receptor for the neurotransmitter acetylcholine and a ligand-gated ion channel. When acetylcholine binds, the receptor changes shape and opens a pore through the cell membrane, allowing positively charged ions, or cations, to pass. This can rapidly change the electrical state of the cell .^1,2

Nicotinic acetylcholine receptors are built from five protein subunits arranged around a central ion-conducting pore. Different combinations of subunits form receptor subtypes with different physiological and pharmacological properties. Broadly, muscle-type receptors occur at skeletal neuromuscular junctions, while neuronal nicotinic receptors are found throughout the central and peripheral nervous systems .¹

At the neuromuscular junction, acetylcholine released from a motor neuron binds to nicotinic receptors concentrated on the motor end plate of a skeletal muscle fiber. Opening of these receptors produces cation movement, including sodium entry, with a net depolarizing effect on the muscle membrane that creates an end-plate potential. If this depolarization reaches threshold, voltage-gated sodium channels in the surrounding membrane generate a muscle action potential that ultimately leads to contraction .²

Nicotinic receptors are distinct from muscarinic acetylcholine receptors. Both respond to acetylcholine, but nicotinic receptors are ion channels that produce relatively rapid electrical responses, whereas muscarinic receptors are G protein-coupled receptors that influence cells through intracellular signaling pathways. The term nicotinic comes from the ability of nicotine to activate members of this receptor family and does not mean that nicotine is their normal physiological messenger .¹