GABA_A Receptors and the Diversity in their Structure and Pharmacology

GABA_A receptors (GABA_ARs) are a class of ligand-gated ion channels with high physiological and therapeutic significance. In the brain, these pentameric receptors occur with diverse subunit composition, which confers highly complex pharmacology to this receptor class. An impressive range of clinically used therapeutics are known to bind to distinct sites found on GABA_ARs to modulate receptor function. Numerous experimental approaches have been used over the years to elucidate the binding sites of these drugs, but unequivocal identification is challenging due to subtype- and ligand-dependent pharmacology. Here, we review the current structural and pharmacological understanding of GABA_ARs, besides highlighting recent evidence which has revealed greater complexity than previously anticipated.