Different contributions of GABAA and GABAC receptors to rod and cone bipolar cells in a rat retinal slice preparation

Whole cell currents were recorded from rod and cone bipolar cells in a slice preparation of the rat retina. Use of the gramicidin D perforated-patch technique prevented loss of intracellular compounds. The recorded cells were identified morphologically by injection with Lucifer yellow. During the recordings, the cells were isolated synaptically by extracellular cobalt. To distinguish the gamma-aminobutyric acid (GABA) receptors pharmacologically, the GABA(A) receptor antagonist, bicuculline, and the GABA(C) receptor antagonist, 3-aminopropyl(methyl) phosphinic acid, were used. In all bipolar cells tested, application of GABA induced postsynaptic chloride currents that hyperpolarized the cells from their resting potential of about -40 mV. GABA was applied at different concentrations to allow for the different affinity of GABA at GABA(A) and GABA(C) receptors. At a GABA concentration of 25 mu M, in the case of rod bipolar cells, similar to 70% of the current was found to be mediated by GABA(C) receptors. In the case of cone bipolar cells, only similar to 20% of the current was mediated by GABA(C) receptors. Furthermore, this GABA(C)-mediated fraction varied among the different morphological types of cone bipolar cells, supporting the hypothesis of distinct functional roles for the different types of cone bipolar cells. There is evidence that the efficacy of GABA(C) receptors is modulated by glutamate through metabotropic glutamate receptors. We tested this hypothesis by applying agonists of metabotropic glutamate receptors (mGluR)1/5 to rod bipolar cells. The specific agonist (+/-)-trans-azetidine-2,4-dicarboxylic acid and the potent mGluR agonist quisqualic acid reduced the amplitude of the GABA(C) responses by 10-30%. This suggests a functional role for the modulation of GABA(C) receptors by the metabotropic glutamate receptors mGluR1/5.