GabaA Receptors: Pharmacology, Behavioral Roles, and Motor Disorders

Abstract

τ-Aminobutyric acid (GABA), the most prevalent inhibitory neurotransmitter in the mammalian brain, exerts its main action through GABAA receptors. They belong to the superfamily of ligand-gated ion channels and respond to GABA by the opening of an intrinsic anion channel. Multiple GABAA receptor subtypes in the brain show differential regional and developmental expression patterns. The receptors have a pentameric structure and are formed from members of at least three different subunit families (α1–6, β1–3, and τ1–3). The regulation of functional properties by GABA and its analogs and by benzodiazepine (BZ) receptor ligands differs dramatically with the type of α variant in the receptor complex. Additional variations of GABAA receptors result from substitution of γ subunits. The role of the β subunits, which are essential for receptor assembly, is less well defined on a functional basis. Besides their involvement in anxiolysis and sedation, GABAA receptors clearly have an impact on motor coordination. However, with the possible exception of the alcohol-and BZ-sensitive alcohol non-tolerant (ANT) rat line, it is not well documented whether a genetic alteration in this receptor system is directly involved in the impairment of animal or human motor activity.