Alpha-9 alpha-10 nicotinic acetylcholine receptor (α9α10 nAChR)

The Alpha-9 alpha-10 nicotinic acetylcholine receptor (α9α10 nAChR) is a pentameric ligand-gated ion channel composed of α9 and α10 subunits. It is predominantly expressed in sensory hair cells of the cochlea, where it mediates synaptic transmission between efferent cholinergic medial olivocochlear fibers and hair cells, regulating auditory sensitivity and protecting against noise-induced hearing loss[1][7]. Unlike most nicotinic receptors, α9α10 has a highly restricted tissue distribution, unusual pharmacology (including inhibition—not activation—by nicotine), and unique subunit assembly requirements[1][4]. It is also expressed in immune cells, implicating roles in inflammation. The receptor is pharmacologically targeted by several peptide antagonists (notably α-conotoxins) derived from cone snail venom, showing analgesic efficacy in animal models of neuropathic pain[2][4][5]. As a validated therapeutic target, it is under active investigation for drug development aimed at treating hearing loss, tinnitus, and chronic pain[6].

Other names

α9α10 nAChRalpha9alpha10 nicotinic acetylcholine receptorhair cell nicotinic acetylcholine receptor

Drugs targeting this receptor primarily act via competitive antagonism (e.g., α-conotoxins, α-bungarotoxin, snake venom peptides) or negative allosteric modulation (certain toxins). Potential positive allosteric modulation is also under investigation.