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

In recent years, the complexity of the GABA_A receptor, both with respect to subunit heterogeneity and its multiple interacting binding sites, has become apparent. Mutagenesis techniques, combined with biochemical and electrophysiological analysis, are beginning to provide information on structure-function relationships of this important neurotransmitter receptor. By integrating information from studies of the GABA_AR and other members of the LGIC superfamily, initial attempts have been made to model receptor-ligand interactions and their consequences on channel activity (see Section 7). While these models provide a useful framework in which to envision receptor structure and function, none are able to reconcile all of the experimental data on the binding and gating of the GABA_AR. At this point, it is impossible to develop a model to explain all of the complex allosteric interactions that occur at this receptor, particularly in view of the sometimes subtle differences in pharmacological properties that are displayed by different GABA_A receptor subtypes. This will ultimately require the elucidation of the complete three dimensional structure of individual receptor subtypes at the atomic level and more extensive characterization of their various ligand binding sites.