Neuronal nicotinic acetylcholine receptor alpha-4 beta-4 subtype (α4β4 nAChR) (α4β4 nAChR)

The neuronal nicotinic acetylcholine receptor alpha-4 beta-4 (α4β4) subtype is a heteropentameric ligand-gated ion channel belonging to the Cys-loop superfamily (Gotti et al., 2006 [1]). It is composed of α4 (CHRNA4) and β4 (CHRNB4) subunits, forming a cation-selective pore that mediates fast excitatory neurotransmission in response to acetylcholine (IUPHAR/BPS Guide to Pharmacology [2]). While less abundant than the α4β2 subtype in the brain, α4β4 receptors are expressed in specific regions like the medial habenula and autonomic ganglia, where they modulate the release of neurotransmitters such as dopamine and glutamate (UniProt P43681 [3]). This receptor is a significant target in nicotine addiction research, as it contributes to the rewarding effects of nicotine and the physical symptoms of withdrawal (Changeux, 2010 [4]). Pharmacological agents such as varenicline and cytisine act as partial agonists at this site, aiding in smoking cessation by reducing nicotine cravings (PubChem CID 5310966 [5]). However, the structural similarity between α4β4 and other nicotinic subtypes poses challenges for drug selectivity, often leading to off-target effects in the cardiovascular and gastrointestinal systems (Zoli et al., 2015 [6]).

Other names

alpha4beta4 nicotinic receptorCHRNA4-CHRNB4 receptorNicotinic acetylcholine receptor alpha4beta4Neuronal acetylcholine receptor subunit alpha-4/beta-4 complex

Agonist, partial agonist, or antagonist modulation of cation-selective channel activity