Cholinergic receptor nicotinic alpha 9 subunit (CHRNA9) (CHRNA9)

The alpha9-nicotinic acetylcholine receptor (alpha9-nAChR) is a member of the Cys-loop family of ligand-gated ion channels, primarily forming homomeric or heteromeric complexes with the alpha10 subunit (UniProt Q9UGM1). Unlike most other nicotinic receptors, alpha9-nAChR exhibits a unique pharmacological profile where nicotine acts as an antagonist rather than an agonist, and it is sensitive to both nicotinic and muscarinic ligands (PubMed 11752216). It is highly expressed in the sensory hair cells of the inner ear, where it mediates inhibitory efferent feedback from the brainstem to modulate auditory sensitivity and protect against noise-induced damage (PubMed 12697997). Beyond the auditory system, the receptor is found in immune cells, keratinocytes, and various cancer tissues, playing roles in inflammation and tumor progression (PubMed 25282151). In the context of disease, alpha9-nAChR has emerged as a promising therapeutic target for the treatment of chronic neuropathic pain and certain malignancies, such as triple-negative breast cancer and lung cancer (PubMed 35058614). Selective antagonists, including various alpha-conotoxins like RgIA and Vc1.1, are being investigated for their ability to provide analgesia and inhibit tumor growth by blocking the receptor's signaling pathways (PubMed 19721015).

Other names

Neuronal acetylcholine receptor subunit alpha-9nAChR alpha-9NACHRA9alpha9-nAChRHSA243342

The alpha9-nAChR functions as a ligand-gated cation channel with high permeability to calcium (UniProt Q9UGM1). Therapeutic strategies primarily involve the use of selective antagonists to block the receptor's activity in the dorsal root ganglia and immune cells to alleviate neuropathic pain and inflammation (PubMed 19721015). In oncology, antagonism of the receptor inhibits mitogenic signaling pathways, such as AKT, ERK, and STAT3, that drive tumor cell proliferation and metastasis (PubMed 35058614).