DIFFERENTIAL PHARMACOLOGY OF GAGA(A) AND GABA(C) RECEPTORS ON RAT RETINAL BIPOLAR CELLS

GABA(A) and GABA(C) receptors were studied on cultured or freshly isolated rat retinal bipolar cells. The cells displayed GABA-induced whole-cell currents, which were only partially blocked by high concentrations (100 mu M) of the GABA(A) receptor antagonist bicuculline. The bicuculline-resistant (GABA(C)) component was insensitive to the GABA(A) receptor modulators flunitrazepam (1 mu M) and pentobarbital (50 mu M). The bicuculline-sensitive portion of the current was strongly augmented by both drugs, indicating that it was mediated by conventional GABA(A) receptors. The GABA(C) and GABA(A) receptor subtypes displayed a 7-fold difference in their binding affinity for GABA, the EC(50) values being 4.2 mu M and 27.1 mu M, respectively. The Hill coefficient was similar to 2 for both receptors. The bicuculline-insensitive GABA(C) receptors were markedly blocked by 100 mu M picrotoxinin, 2-(3-carboxypropyl)-3-amino-6-(4-methoxyphenyl)pyridazinium bromide (SR-95531) and gamma-hexachlorocyclohexane, drugs known to be antagonists of GABA(A) receptors. Examination of single-channel currents indicated main-state conductances of 7.9 pS and 29.6 pS for GABA(C) and GABA(A) receptors, respectively. The pore diameter of open GABA(C) receptor channels was 5.1 Angstrom, i.e. close to the value of 5.6 Angstrom reported for the GABA(A) receptor. These results demonstrate that rod bipolar cells possess two populations of pharmacologically distinct GABA receptors, GABA(A) and novel-type GABA(C) receptors, which might subserve different physiological functions in controlling visual transduction in the retina.