MODULATION OF GABA(C) RECEPTORS IN RAT RETINAL BIPOLAR CELLS BY PROTEIN-KINASE-C

1. The intracellular phosphorylation of bicuculline- and baclofen-inse nsitive GABA(c), receptors was investigated in rat retinal bipolar cel ls. The cells were recorded in organotypic slice cultures by using the whole-cell configuration of the patch-clamp technique. 2. Peak GABA r esponses recorded in the presence of bicuculline decreased with repeti tive GABA applications. Intracellular application of the phorbol ester , phorbol 12-myristate, 13-acetate (PMA) increased this run-down, whil st it was prevented by both tamoxifen and phosphatase. 3. Perfusing th e cells extracellularly with L-AP4, trans-(+/-)-1-amino-1,3-cyclopenta ne dicarboxylate (ACPD) or a-methyl serotonin accelerated the run-down of GABA, responses. 4. Modulation of GBBA(c) responses could be induc ed by intracellular application of GTP gamma S, indicating involvement of G-proteins in the transduction cascade. 5. These results suggest t hat retinal GABA(c), receptors in bipolar cells are modulated by prote in kinase C. Receptors which stimulate phospholipase C, presumably via G(i) or G(o), such as some of the metabotropic glutamate receptors or the 5-HT2 receptor, appear to be linked to this regulatory pathway.