Nicotinic acetylcholine receptor (nAChR), adult skeletal muscle type (nAChR)

The adult skeletal muscle nicotinic acetylcholine receptor (nAChR) is a pentameric, ligand-gated ion channel situated at the postsynaptic membrane of the neuromuscular junction (StatPearls, 2023). It is composed of five subunits—two alpha-1, one beta-1, one delta, and one epsilon—which distinguish it from the fetal isoform that contains a gamma subunit instead of epsilon (UniProt, 2024). The receptor's primary function is to mediate fast synaptic transmission by opening a cation-selective pore in response to the binding of acetylcholine, leading to membrane depolarization and subsequent muscle contraction (NIH, 2023). Clinically, this receptor is the primary target for neuromuscular blocking agents used in surgical anesthesia to induce muscle relaxation and facilitate endotracheal intubation (PubMed, 2022). It is also the central site of pathology in Myasthenia Gravis, an autoimmune disorder where antibodies target the receptor, and in various congenital myasthenic syndromes caused by genetic mutations in its subunits (Wikipedia, 2024). Furthermore, the receptor plays a role in maintaining muscle mass by regulating the expression of connexin hemichannels (NIH, 2023).

Other names

Muscle-type nicotinic acetylcholine receptorAdult muscle nAChRNeuromuscular nicotinic receptorCHRNA1/CHRNB1/CHRND/CHRNE complexAChREndplate acetylcholine receptor

Drugs targeting this receptor act as either depolarizing agonists (e.g., succinylcholine) that cause persistent membrane depolarization or non-depolarizing competitive antagonists (e.g., rocuronium) that prevent acetylcholine binding, both resulting in neuromuscular blockade. Additionally, acetylcholinesterase inhibitors increase the concentration of the endogenous ligand, acetylcholine, to overcome competitive blockade or compensate for receptor loss in disease.