Neuronal nicotinic acetylcholine receptor (nAChR)

Neuronal nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that mediate fast excitatory synaptic transmission and modulate the release of various neurotransmitters throughout the central and peripheral nervous systems [5, 6, 11]. These receptors are composed of diverse combinations of alpha (α2–α10) and beta (β2–β4) subunits, which determine their unique pharmacological profiles and physiological roles [11, 12]. The α2-containing subtypes, encoded by the CHRNA2 gene, are specifically localized in inhibitory interneuron populations such as Martinotti cells in the cortex and OLM cells in the hippocampus, where they regulate network synchronization and cognitive processes [1, 2, 4]. Dysregulation or genetic mutations in these receptors are linked to several neurological conditions, including autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), Alzheimer’s disease, and nicotine dependence [2, 5, 15]. Pharmacological targeting of nAChRs involves agonists and partial agonists to enhance cognitive function or aid in smoking cessation, as well as antagonists for managing epilepsy and pain [1, 9, 10]. Recent research also highlights the role of α2-containing receptors in non-neuronal tissues, such as beige adipocytes, where they influence systemic energy metabolism and thermogenesis [2, 3].

Other names

Neuronal acetylcholine receptorNicotinic cholinergic receptoralpha-2 containing nicotinic receptorCHRNA2-containing nAChRalpha2-beta2 nicotinic receptoralpha2-beta4 nicotinic receptor

Agonist, Partial agonist, Antagonist, Positive allosteric modulator