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.