Neuronal acetylcholine receptor subunit alpha-4 (CHRNA4) (CHRNA4)

The Neuronal acetylcholine receptor subunit alpha-4 (CHRNA4) is a critical component of the most prevalent nicotinic acetylcholine receptor (nAChR) subtype in the human brain, typically forming heteropentameric ion channels with beta-2 subunits (UniProt: P43681). These receptors function as ligand-gated cation channels that facilitate fast excitatory neurotransmission and modulate the release of other neurotransmitters like dopamine and glutamate, thereby influencing cognition, mood, and reward pathways (PubMed: 25833123). CHRNA4 is a primary therapeutic target for smoking cessation, as its interaction with nicotine mediates the drug's addictive properties (PubChem: 89594). Genetic variations in this subunit are significantly associated with Autosomal Dominant Sleep-related Hypermotor Epilepsy (ADSHE), highlighting its role in maintaining cortical excitability (PubMed: 7566090). Pharmacological agents targeting CHRNA4 include partial agonists like varenicline, which reduce nicotine withdrawal symptoms, and positive allosteric modulators like galantamine used in Alzheimer's disease treatment (StatPearls: NBK547661). Beyond addiction and epilepsy, the receptor is being investigated for its potential roles in treating neurodegenerative diseases and cognitive impairment (PubMed: 17005051).

Other names

Cholinergic receptor nicotinic alpha 4 subunitNicotinic acetylcholine receptor alpha 4NACRA4EBN1BFNC

Agonist, partial agonist, or antagonist binding to the extracellular ligand-binding site, or allosteric modulation, to regulate the opening of the cation-selective pore.