Molecular composition of GABA(C) receptors

In 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 GABA(A) and a recently identified type, GABA(C), have integral chloride channels, whereas GABA(B) receptors couple to separate K⁺ or Ca²⁺ channels via G-proteins. By analogy to nicotinic acetylcholine receptors, native GABA(A) receptors are believed to be heterooligomers of five subunits, drawn from five classes (α, β, γ, δ, ε/%). An additional class, called ρ, is often categorized with GABA(A) receptor subunits due to a high degree of sequence similarity. However, ρ subunits are capable of forming functional homooligomeric and heterooligomeric receptors, whereas GABA(A) receptors only express efficiently as heterooligomers. Intriguingly, the pharmacological properties of receptors formed from ρ subunits are very similar to those exhibited by GABA(C) receptors and ρ subunits and GABA(C) responses have been colocalized to the same retinal cells, indicating that ρ subunits are the sole components of GABA(C) receptors. In contrast, the propensity of GABA(A) receptor and ρ subunits to form multimeric structures and their coexistence in retinal cells suggests that GABA(C) receptors might be heterooligomers of ρ and GABA(A) receptor subunits. This review will summarize our current understanding of the molecular composition of GABA(C) receptors based upon studies of ρ subunit assembly.