Molecular composition of GABAC receptors

AbstractIn the central nervous system inhibitory neurotransmission is primarily achieved through activation of receptors for γ-aminobutyric acid (GABA). Three types of GABA receptors have been identified on the basis of their pharmacology and electrophysiology. The predominant type, termed GABAA and a recently identified type, GABAC, have integral chloride channels, whereas GABAB receptors couple to separate K+ or Ca2+ channels via G-proteins. By analogy to nicotinic acetylcholine receptors, native GABAA receptors are believed to be heterooligomers of five subunits, drawn from five classes (α, β, γ, δ, ϵ/χ). An additional class, called ρ, is often categorized with GABAA receptor subunits due to a high degree of sequence similarity. However, ρ subunits are capable of forming functional homooligomeric and heterooligomeric receptors, whereas GABAA receptors only express efficiently as heterooligomers. Intriguingly, the pharmacological properties of receptors formed from ρ subunits are very similar to those exhibited by GABAC receptors and ρ subunits and GABAC responses have been colocalized to the same retinal cells, indicating that ρ subunits are the sole components of GABAC receptors. In contrast, the propensity of GABAA receptor and ρ subunits to form multimeric structures and their coexistence in retinal cells suggests that GABAC receptors might be heterooligomers of ρ and GABAA receptor subunits. This review will summarize our current understanding of the molecular composition of GABAC receptors based upon studies of ρ subunit assembly