alpha4

Alpha4, or alpha-4, most commonly refers to the alpha-4 subunit of neuronal nicotinic acetylcholine receptors (nAChRs). The protein is encoded by the CHRNA4 gene in humans. Neuronal nAChRs are pentameric ion channels that mediate fast synaptic transmission in the central nervous system and peripheral circuits. The alpha-4 subunit can assemble with other subunits, most notably beta-2, to form high-affinity receptors such as alpha4beta2, which are abundant in brain regions involved in cognition and reward and are activated by acetylcholine as well as nicotine.

Genetic and clinical relevance: CHRNA4 is located on chromosome 20q13.12. Variants and rare mutations in CHRNA4 have been associated with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and may influence susceptibility to nicotine dependence and other neuropsychiatric traits.

Structure and function: Each subunit has a ligand-binding extracellular domain followed by four transmembrane segments (M1–M4). When assembled, these subunits form a pore that conducts cations, contributing to neuronal excitability and neurotransmitter release. The alpha-4/beta-2 receptor has high affinity for nicotine and plays a major role in synaptic plasticity and attention.

Other uses: In software development, “alpha4” can denote the fourth alpha release of a project, indicating an early testing stage prior to beta versions. The term may also appear as a model name or designation in various technical contexts.