Nicotinic acetylcholine receptor α9α10 subtype (α9α10 nAChR)

The nicotinic acetylcholine receptor α9α10 subtype (α9α10 nAChR) is a heteropentameric ligand-gated ion channel primarily composed of α9 and α10 subunits, forming stoichiometries such as (α9)2(α10)3 or (α9)3(α10)2, and is highly expressed in cochlear and vestibular hair cells, immune cells, dorsal root ganglia, and select brain regions including frontal cortex, hippocampus, and medulla oblongata. It mediates central nervous system control of auditory and vestibular sensory processing through acetylcholine binding, which induces Ca2+ influx, activation of Ca2+-dependent K+ (SK2) channels, and hair cell hyperpolarization, distinguishing it from other nAChRs by its antagonism by nicotine and block by strychnine or bicuculline. Unlike most nAChRs, functional α9α10 assembly strictly requires ligand binding (e.g., ACh or antagonists like α-Bgtx) for surface expression. In disease, it contributes to noise-induced hidden hearing loss and presbycusis via efferent innervation of outer hair cells, with upregulated expression in knockout models suggesting compensatory roles with α7 nAChRs. Therapeutically, potent antagonists like α-conotoxin RgIA bind selectively at α9 interfaces, offering potential for chronic pain treatment by inhibiting this receptor in sensory neurons. Its unique pharmacology and restricted expression profile make it an attractive drug target, though challenges include avoiding auditory side effects.

Other names

α9α10 nicotinic acetylcholine receptorneuronal acetylcholine receptor α9α10nAChR α9α10

Selective antagonism at α9(+)/α9(−) or α10(+)/α9(−) binding sites (e.g., RgIA blocks channel opening), Agonism by acetylcholine leading to Ca2+ influx and SK2 channel activation/hyperpolarization, Ligand-dependent assembly and surface expression