Nicotinic

Nicotinic refers to nicotinic acetylcholine receptors (nAChRs), a family of ligand-gated ion channels that mediate fast synaptic transmission in both the peripheral and central nervous systems. They are activated by acetylcholine and by nicotine, and they belong to the Cys-loop superfamily of pentameric receptors. Activation opens a cation-selective pore, allowing influx of sodium and calcium and efflux of potassium, which typically excites the postsynaptic cell.

nAChRs are found in two major tissue groups with distinct subunit compositions. Muscle-type receptors at the neuromuscular junction are pentamers that usually include two α1 subunits along with β1, δ, and either γ or ε subunits, depending on developmental stage. Neuronal-type receptors are more diverse, assembled from various combinations of α (such as α2–α7, and α9), β (β2–β4), and other subunits, and they reside in many brain regions as well as autonomic ganglia. Different subtypes exhibit unique pharmacology, distribution, and desensitization kinetics, contributing to roles in attention, learning, reward, and neuromuscular signaling.

Pharmacology and clinical relevance: endogenous acetylcholine activates nAChRs; nicotine from tobacco products also acts as an agonist, with varying effects depending on subtype and desensitization state. Pharmacological agents include antagonists such as curare-derived compounds and alpha-bungarotoxin, as well as clinical neuromuscular blockers that target nAChRs. Therapeutically, nicotine-related drugs (for example, varenicline and cytisine) modulate specific receptor subtypes to aid smoking cessation. Pathophysiology includes autoimmune or genetic disorders affecting nAChR function, such as myasthenia gravis and certain congenital myasthenic syndromes, which disrupt neuromuscular transmission and cause muscle weakness.