The GABAA Receptor Family: Molecular and Functional Diversity

Abstract

Fast excitatory and inhibitory signal transmission in the central nervous system (CNS) is mediated, in large part, by ion channels gated by amino acids and their derivatives (Dingledine et al. 1988). Many of these channels are built to a common design (Unwin 1989) of which the prototype is the nicotinic acetylcholine receptor (Changeux et al. 1984). The receptors/channels are assembled from several homologous subunits to form allosterically interacting transmembrane glycoprotein complexes. The main inhibitory channel is constituted by the GABAA receptor, which occurs in virtually every neuron in the brain; it is estimated that approximately one third of all synapses in the CNS are GABAergic (Bloom and Iversen 1971). Notably, the GABAA receptor (Olsen and Venter 1986; Stephenson 1988; Olsen and Tobin 1990) is the site of action of anxiolytics, anticonvulsants, hypnotics, anesthetics, and muscle relaxants, and hence knowledge of its structural and functional diversity is of pivotal interest to...