Subunit Composition and Structure of GABAA-Receptor Subtypes.

γ-Aminobutyric acid (GABAA) receptors are the major inhibitory neurotransmitter receptors in the brain and are the site of action of many clinically important drugs. They are made up of five subunits that can belong to eight different subunit classes. Depending on their subunit composition these receptors exhibit distinct pharmacological and electrophysiological properties. The distinct but overlapping regional and cellular distribution of these subunits gives rise to the formation of a large number of GABAA-receptor subtypes, only a few of which so far have been unequivocally identified in the brain. Recent homology modeling of the structure of the extracellular and transmembrane domain of GABAA receptors for the first time provided a glimpse on the three-dimensional organization of this receptor, and placed different protein segments that have been shown to be of functional importance into a "region in space" and into defined neighboring relations. The models obtained could explain experimental observations and propose the location of putative drug-binding sites. They can be now used to design experiments for clarification of pharmacological and structural questions as well as to shed light on conformational changes during binding of agonist, gating, and allosteric modulation of these receptors. [ABSTRACT FROM AUTHOR]