The Structure and Expression of the GABAA Receptor as Deduced by Molecular Genetic Studies
It is well established that the inhibitory neurotransmitter γ-aminobutyric acid (GABA) mediates many of its effects by binding to the GABAA receptor, which is present on the majority of mammalian brain neurons (Enna, 1983), resulting in the opening of an integral chloride channel. This receptor has considerable pharmaceutical importance as it contains binding sites for anti-convulsant (barbiturates), anxiogenic (β-carbolines) and convulsant (picrotoxin) drugs (reviewed in Turner and Whittle, 1983; Olsen and Venter, 1986). Although it is known that anxiolytic agents such as benzodiazepines also bind to the GABAA receptor, there exists a population of benzodiazepine-insensitive receptors (Study and Barker, 1981; Unnerstall et al., 1981; de Bias et al., 1988). Our understanding of the molecular structure and function of this receptor complex has been greatly increased by the application of recombinant DNA methodology and the subsequent cloning and expression of cDNA clones that encode its constituent subunits. This chapter will review these advances and describe some recent results arising from the use of the cloned sequences.
KeywordsGABAA Receptor Receptor Subunit Xenopus Oocyte Gaba Receptor Glycine Receptor
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