There is increasing evidence that GABAC receptors are composed of GABA rho subunits. In this study, we compared the properties of native GABAC receptors with those of receptors composed of a GABA rho subunit. A homologue of the GABA rho 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 rho 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 GABAC 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 microM, a value similar to that reported for GABAC receptors. Pharmacologically, the responses were bicuculline insensitive and not modulated by either diazepam or pentobarbital as is the case for GABAC receptors. There were, however, some distinct differences between native GABAC 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 GABAC receptors. We conclude that GABAC receptors are formed by GABA rho subunits but that native GABAC receptors probably consist of a mixture of GABA rho subunits.