[Frontiers in Bioscience 1, d214-233, September 1, 1996]
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MOLECULAR BIOLOGY OF THE GABAA RECEPTOR: FUNCTIONAL DOMAINS IMPLICATED BY MUTATIONAL ANALYSIS

Martin Davies1, Alan N. Bateson1,2 and Susan M. J. Dunn1,2

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

8. CONCLUSIONS

In recent years, the complexity of the GABAA 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 GABAAR 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 GABAAR. 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 GABAA 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.

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