units encoded by different genes which respond to the same neurotransmitter and produce the same biophysical response, albeit with different affinities, kinetics and drug sensitivities (1:2). The subunits are named (, (, (, ( and ( according to the degree of sequence homology between them, for example ( subunits share 70% homology with each other but only 25% homology with ( subunits. The identification of six (, four (, four (, one ( and two ( subunits and splicing variants of many of them suggests that these receptors have a diversity of biological roles and raises the possibility of designing selective drug therapies for the treatment of insomnia, epilepsy and anxiety.
The function, composition and GABA binding potential of native GABAA subunit combinations and their associated polypepetides has recently been investigated using affinity labeling, microsequencing, site directed mutagenesis and domain specific localization. Single point mutations at amino acid Phe64 in the N-terminal extracellular domain of the ( subunit results in a reduction in agonist and antagonist affinities when co-expressed with (2 and (2 subunits. This position is also covalently modified using the GABA site photoaffinity agonist [3H]muscimol. Similar labeling (inferring similar sequence) is present in all ( subunits, (2 and the ( subunit, b
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