Martin Davies¹, Alan N. Bateson^1,2 and Susan M. J. Dunn^1,2

¹ Department of Pharmacology

²Division of Neuroscience, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2H7

Received 07/16/96; Accepted 07/22/96; On-line 09/01/96

GABA_A receptors are the major inhibitory neurotransmitter receptors in mammalian brain. They belong to a family of ligand-gated ion channels that also includes the nicotinic acetylcholine receptors, glycine receptors and 5HT₃ receptors. Each receptor in the family is believed to be a pentamer of homologous subunits that assemble to form a central transmembrane ion pore which, in the case of the GABA_A receptor, is anion-selective. For almost twenty years, there has been tremendous interest in the structure and function of GABA_A receptors, not only because of their importance in regulating brain excitability but also because these proteins are the specific targets for a wide variety of therapeutic agents including the anxiolytic benzodiazepines and barbiturates. Molecular cloning has revealed that GABA_A receptors are heterogeneous, being formed by combinations of different isoforms of several subunit classes (alpha, ß, gamma, delta). The physiological and pharmacological properties of individual GABAA receptor subtypes appear to depend on their precise subunit complement. In this review, we focus on the application of modern techniques in molecular biology, particularly mutational analysis, to identify structural domains of these receptors that are important for ligand recognition and receptor function.