A comparison of GABA(C) and ρ subunit receptors from the white perch retina

There is increasing evidence that GABA(C) receptors are composed of GABA ρ subunits. In this study, we compared the properties of native GABA(C) receptors with those of receptors composed of a GABA ρ subunit. A homologue of the GABA ρ gene was cloned from a white perch (Roccus americana) retinal cDNA library. The clone (perch-s) has an open reading frame of 1422 nucleotide base pairs and encodes a predicted protein of 473 amino acids. It is highly homologous to GABA ρ subunits cloned from human and rat retinas. The receptors (perch-s receptor) expressed by this gene in Xenopus oocytes show properties similar to those of the GABA(C) receptors present on white perch retinal neurons. GABA induced a sustained response that had a reversal potential of -27.1 ± 3.6 mV. The EC₅₀ for the response was 1.74 ± 1.25 μM, a value similar to that reported for GABA(C) receptors. Pharmacologically, the responses were bicuculline insensitive and not modulated by either diazepam or pentobarbital as is the case for GABA(C) receptors. There were, however, some distinct differences between native GABA(C) and perch-s receptors. I4AA acts as a partial agonist on perch-s receptors whereas it is strictly an antagonist on native GABAc receptors. Picrotoxin inhibition is noncompetitive on perch-s receptors, but both competitive and noncompetitive on GABA(C) receptors. We conclude that GABA(C) receptors are formed by GABA ρ subunits but that native GABA(C) receptors probably consist of a mixture of GABA ρ subunits.