Muscle nicotinic acetylcholine receptor (nAChR (muscle-type))

The muscle nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel heteropentamer located at the postsynaptic membrane of the neuromuscular junction (NMJ), essential for translating motor neuron action potentials into muscle contraction.[1][3][5] It consists of two α1 subunits, one β1, one δ, and either γ (fetal isoform) or ε (adult isoform), forming two acetylcholine (ACh) binding sites at α-γ/δ interfaces that trigger rapid Na+/K+ influx upon activation, generating the endplate potential.[1][3][5] Fetal and adult isoforms differ in conductance and developmental expression, with the γ-to-ε switch occurring postnatally to support mature single-fiber innervation.[1] Dysregulation underlies myasthenia gravis, an autoimmune disorder where antibodies target the receptor, impairing NMJ signaling and causing muscle weakness.[3] Therapeutically, it is targeted by neuromuscular blockers for anesthesia-induced paralysis, though this risks respiratory failure if not reversed.[3][4][7] Structural studies from Torpedo electric organ reveal a pseudo-fivefold symmetric architecture with extracellular ACh sites, a transmembrane pore gate, and intracellular domains interacting with clustering proteins like rapsyn.[3]

Other names

Muscle-type nicotinic acetylcholine receptorMuscle nAChRNeuromuscular nicotinic acetylcholine receptorSkeletal muscle nicotinic receptor

Competitive antagonism at acetylcholine binding sites, blocking channel opening and preventing muscle depolarization; Non-competitive blockade or channel modulation leading to muscle relaxation