I4AA-sensitive chloride current contributes to the center light responses of bipolar cells in the tiger salamander retina

Light-evoked currents in depolarizing and hyperpolarizing bipolar cells (DB Cs and HBCs) were recorded under voltage-clamp conditions in living retinal slices of the larval tiger salamander. Responses to illumination at the ce nter of the DBCs' and HBCs' receptive fields were mediated by two postsynap tic currents: Delta I-C, a glutamate-gated cation current with a reversal p otential near 0 mV, and DI Cl, a chloride current with a reversal potential near -60 mV. In DBCs Delta I-C was suppressed by L-2-amino-4-phosphonobuty ric acid (L-AP4), and in HBCs it was suppressed by 6,7-dinitroquinoxaline2, 3- dione (DNQX). In both DBCs and HBCs Delta I-Cl was suppressed by imidazo le-4-acetic acid (I4AA), a GABA receptor agonist and GABA(C) receptor antag onist. In all DBCs and HBCs examined, 10 mu M I4AA eliminated Delta I-Cl an d the light-evoked current became predominately mediated by Delta I-C. The addition of 20 mu M L-AP4 to the DBCs or 50 mu M DNQX to HBCs completely ab olished Delta I-C. Focal application of glutamate at the inner plexiform la yer elicited chloride currents in bipolar cells by depolarizing amacrine ce lls that release GABA at synapses on bipolar cell axon terminals, and such glutamate-induced chloride currents in DBCs and HBCs could be reversibly bl ocked by 10 mM I4AA. These experiments suggest that the light-evoked, I4AA- sensitive chloride currents (Delta I-Cl) in DBCs and HBCs are mediated by n arrow field GABAergic amacrine cells that activate GABA(C) receptors on bip olar cell axon terminals. Picrotoxin (200 mu M) or (1,2,5,6-tetrahydropyrid ine-4yl) methyphosphinic acid (TPMPA) (2 other GABA(C) receptor antagonists ) did not block (but enhanced and broadened) the light-evoked Delta I-Cl, a lthough they decreased the chloride current induced by puff application of GABA or glutamate. The light response of narrow field amacrine cells were n ot affected by I4AA, but were substantially enhanced and broadened by picro toxin. These results suggest that there are at least two types of GABA(C) r eceptors in bipolar cells: one exhibits stronger I4AA sensitivity than the other, but both can be partially blocked by picrotoxin. The GABA receptors in narrow field amacrine cells are I4AA insensitive and picrotoxin sensitiv e. The light-evoked Delta I-Cl in bipolar cells are mediated by the more st rongly I4AA-sensitive GABA(C) receptors. Picrotoxin, although acting as a p artial GABA(C) receptor antagonist in bipolar cells, does not suppress Delt a I-Cl because its presynaptic effects on amacrine cell light responses ove rride its antagonistic postsynaptic actions.