Cholinergic receptor nicotinic alpha 3 subunit (CHRNA3) (CHRNA3)

The Cholinergic receptor nicotinic alpha 3 subunit (CHRNA3) is a critical component of pentameric ligand-gated ion channels that mediate fast excitatory neurotransmission in the peripheral and central nervous systems (UniProt P32297). It is most prominently expressed in autonomic ganglia, where it often co-assembles with the beta 4 and alpha 5 subunits to form the alpha3beta4* receptor subtype (NCBI Gene ID: 1136). This receptor plays a pivotal role in regulating autonomic functions and has been heavily implicated in the biology of addiction and tobacco-related diseases. Genetic variants within the CHRNA5-CHRNA3-CHRNB4 gene cluster, particularly the rs16969968 polymorphism, are strongly associated with nicotine dependence, the number of cigarettes smoked per day, and an increased risk of lung cancer and chronic obstructive pulmonary disease (PubMed PMID: 18385676). Pharmacologically, CHRNA3 is targeted by agonists like nicotine and partial agonists like varenicline, which are used in smoking cessation therapies (PubChem). However, because of its essential role in ganglionic transmission, drugs affecting this target can lead to significant off-target effects, including cardiovascular fluctuations and gastrointestinal distress (StatPearls).

Other names

Neuronal acetylcholine receptor subunit alpha-3nAChR alpha 3NACHRA3Cholinergic receptor, nicotinic, alpha 3Locus control region 2LNCR2

Ligand-gated ion channel activation or inhibition; agonists bind to the extracellular domain to trigger a conformational change that opens the pore for cation (Na+, K+, Ca2+) influx, while antagonists block this channel activity (UniProt P32297).