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 isol ated rat retinal bipolar cells. The cells displayed GABA-induced whole -cell currents, which were only partially blocked by high concentratio ns (100 mu M) of the GABA(A) receptor antagonist bicuculline. The bicu culline-resistant (GABA(C)) component was insensitive to the GABA(A) r eceptor modulators flunitrazepam (1 mu M) and pentobarbital (50 mu M). The bicuculline-sensitive portion of the current was strongly augment ed 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) r eceptors were markedly blocked by 100 mu M picrotoxinin, oxypropyl)-3- amino-6-(4-methoxyphenyl)pyridazinium bromide (SR-95531) and gamma-hex achlorocyclohexane, drugs known to be antagonists of GABA(A) receptors . Examination of single-channel currents indicated main-state conducta nces of 7.9 pS and 29.6 pS for GABA(C) and GABA(A) receptors, respecti vely. The pore diameter of open GABA(C) receptor channels was 5.1 Angs trom, i.e. close to the value of 5.6 Angstrom reported for the GABA(A) receptor. These results demonstrate that rod bipolar cells possess tw o populations of pharmacologically distinct GABA receptors, GABA(A) an d novel-type GABA(C) receptors, which might subserve different physiol ogical functions in controlling visual transduction in the retina.