The GABAA Receptors: Structure and Function

In recent years considerable attention has been given to the study of the GABAA receptors. This is because GABA is the major inhibitory neuro-transmitter in the mammalian central nervous system, where the GABA receptors are ubiquitous, playing an important role in the control of neuronal excitability. There are two pharmacological subclasses of GABA receptors. These are the GABAA receptor, a ligand-gated chloride ion channel, whose pharmacology is defined by the competitive antagonism by the plant alkaloid bicuculline; and the GABAB receptor which is bicuculline-insensitive and (-)baclofen-sensitive and the activation of which results in the production of second messengers via interaction with an as yet unknown G protein (for a review see Bowery, 1989; Stephenson and Dolphin, 1989). The GABAA receptor is the most characterized of the two receptor types. This is because it is the site of action of several groups of therapeutically important drugs, such as the benzodiazepines, the barbiturates and some steroids (reviewed in Olsen and Venter, 1986), each of which allosterically modulate GABAA receptor function at distinct binding sites within the receptor protein.