Nicotinic acetylcholine receptor α3α5β4 subtype (nAChR α3α5β4)

The nicotinic acetylcholine receptor α3α5β4 subtype is a heteropentameric, ligand-gated ion channel belonging to the Cys-loop receptor superfamily. It is composed of three specific neuronal subunits: α3, α5, and β4, encoded by the CHRNA3, CHRNA5, and CHRNB4 genes, respectively[9][5][1]. The receptor is widely expressed in the peripheral and central nervous systems, with prominent roles in autonomic ganglia, where it mediates cholinergic neurotransmission critical for cardiovascular, gastrointestinal, and other autonomic functions[1][5]. In the brain, it is implicated in reward, addiction, and drug-seeking behaviors, notably for nicotine and other substance use disorders[2]. Pharmacologically, the α3α5β4 nAChR subtype exhibits unique agonist and antagonist profiles and is targeted by selective molecules such as AT-1001, as well as non-selective agonists like nicotine[2]. Genetic variants in its subunit genes are associated with altered disease risks, particularly for nicotine dependence and certain cardiovascular conditions[9]. Targeting this receptor subtype presents both therapeutic opportunities (e.g., addiction) and challenges, given its peripheral roles and central nervous side effects[2][1].

Other names

α3β4α5 nicotinic acetylcholine receptornAChR α3α5β4neuronal α3α5β4 nicotinic receptorα3/α5/β4 nAChR

Agonists (e.g., nicotine) activate the ion channel, leading to cation influx (Na⁺, K⁺, Ca²⁺) Antagonists (e.g., AT-1001, α-conotoxins) bind and inhibit channel opening, blocking neurotransmission