A COMPARISON OF GABA(C) AND RHO-SUBUNIT RECEPTORS FROM THE WHITE PERCH RETINA

There is increasing evidence that GABA(C) receptors are composed of GA BA rho subunits. In this study, we compared the properties of native G ABA(C) receptors with those of receptors composed of a GABA rho subuni t A homologue of the GABA rho gene was cloned from a white perch (Rocc us americana) retinal cDNA library. The clone (perch-s) has an open re ading frame of 1422 nucleotide base pairs and encodes a predicted prot ein of 473 amino acids. It is highly homologous to GABA rho subunits c loned from human and rat retinas. The receptors (perch-s receptor) exp ressed by this gene in Xenopus oocytes show properties similar to thos e of the GABA(C) receptors present on white perch retinal neurons. GAB A 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 mu M, a value similar to that reported for GABA(C) receptors. Pharmacologically, the responses were bicuculline insensitive and not modulated by either di azepam or pentobarbital as is the case for GABA(C) receptors. There we re, however, some distinct differences between native GABA(C) and perc h-s receptors. I4AA acts as a partial agonist on perch-s receptors whe reas it is strictly an antagonist on native GABA(C) receptors. Picroto xin inhibition is noncompetitive on perch-s receptors, but both compet itive and noncompetitive on GABA(C) receptors. We conclude that GABA(C ) receptors are farmed by GABA rho subunits but that native GABA(C) re ceptors probably consist of a mixture of GABA rho subunits.