Nicotinic acetylcholine receptors and the roles of the alphα7 subunit

Abstract

Nicotinic acetylcholine receptors (nAChR) are members of the Cys-loop superfamily of ligand-gated ion channels that includes glycine, γ-aminobutyric acid (GABA A ), and serotonin receptor channels. The members of the family are defi ned by a similar pentameric structure with fi ve membrane- spanning subunits surrounding a central water-fi lled, cation-selective pore. The nAChRs are further divided into muscle and neuronal types. Muscle nAChRs comprise α1, ß1, γ, and δ or σ subunits in a 2:1:1:1 stoichiometric ratio. Neuronal type nAChRs are composed of differing combinations of a and ß subunits, with nine genes encoding a subunits (a2-10) and three encoding ß subunits (ß2-4). This review focuses on the α7 subunit, which was cloned from the chicken in 1990 and from the rat in 1993. α7 has received waning and waxing attention as its involvement in diseases, including Alzheimer's disease and lung cancer, has been defi ned and redefi ned. For example, recent reports provide increasing evidence for α7's involvement in the pathogenesis of Alzheimer's disease, suggesting that further work is warranted to understand the roles of the α7 subunit normally and in pathophysiology.