Human alpha-3 beta-4 nicotinic acetylcholine receptor (α3β4 nAChR)

The human alpha-3 beta-4 nicotinic acetylcholine receptor (α3β4 nAChR) is a heteromeric, pentameric ligand-gated ion channel that belongs to the nicotinic acetylcholine receptor family within the "Cys-loop" superfamily of neurotransmitter receptors[3][1][7]. It is composed of α3 and β4 subunits and mediates fast excitatory synaptic transmission in autonomic ganglia, linking the central and peripheral nervous systems[6][7]. The receptor is most abundant in the autonomic ganglia and adrenal medulla, but is also expressed in select brain regions involved in reward and addiction[7][6]. Upon activation by acetylcholine or agonist drugs, it conducts cations (mainly Na^+^ and K^+^), leading to depolarization and excitation of post- and presynaptic neurons[7]. Pharmacological targeting of α3β4 nAChRs is investigated for addiction (e.g., nicotine, cocaine), metabolic disease (e.g., diabetes), and other CNS disorders, owing to its role in modulating autonomic and reward-related neurotransmission[5][4][8]. Selective antagonists such as AT-1001 and α-conotoxins represent tool compounds for studying this receptor and potential leads for drug development[2][4][5][1]. Potential therapeutic targeting is complicated by the receptor’s role in essential autonomic functions, which presents both efficacy opportunities and safety challenges.

Other names

Alpha-3 beta-4 nicotinic receptorα3β4 nicotinic receptorGanglion-type nicotinic receptor

Agonists: Bind to and activate the receptor, inducing cation (Na^+, K^+) influx and neuronal excitation Antagonists: Block the receptor, preventing activation by acetylcholine or nicotine, reducing neurotransmission Partial agonists: Bind and partially activate the receptor, potentially leading to functional antagonism or desensitization Negative allosteric modulators: Bind at sites distinct from the acetylcholine binding site and inhibit receptor function