Modulation by Zn2+ of GABA responses in bipolar cells of the mouse retina

The localization of endogenous Zn2+ in the mouse retina was examined histochemically and the inhibitory action of Zn2+ on GABA-induced responses was studied in bipolar cells isolated from the mouse retina. Accumulation of endogenous Zn2+ was detected in photoreceptors, bipolar, and/or amacrine cells by either the bromopyridylazo-diethylaminophenol method or the dithizone method. Under whole-cell recording conditions, GABA induced a Cl- current in isolated bipolar cells. The current consisted of two components. The first component was inhibited completely by application of 100 microM bicuculline, suggesting that this is a GABA(A)-receptor mediated current. The second component was inhibited completely by 100 microM 3-aminopropyl-(methyl)-phosphinic acid, suggesting that this is a GABA(C)-receptor mediated current. GABA(C) receptors were present at a higher density on the axon terminal than on dendrites. Zn2+ inhibited both GABA(A) and GABA(C) receptors. GABA(C) receptors were more susceptible to Zn2+; the IC50 for the GABA(A) receptor was 67.4 microM and that for the GABA(C) receptor was 1.9 microM. These results suggest that Zn2+ modulates the inhibitory interaction between amacrine and bipolar cells, particularly that mediated by the GABA(C) receptor.