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

The localization of endogenous Zn2+ in the mouse retina was examined histoc hemically and the inhibitory action of Zn2+ on GABA-induced responses was s tudied in bipolar cells isolated from the mouse retina. Accumulation of end ogenous Zn2+ was detected in photoreceptors, bipolar, and/or amacrine cells by either the bromopyridylazo-diethylaminophenol method or the dithizone m ethod. 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 mu M bicuculline, suggesting that this is a GABA(A)-receptor mediated current. The second co mponent was inhibited completely by 100 mu M 3-aminopropyl-(methyl)-phosphi nic 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) rece ptors were more susceptible to Zn2+; the IC50 for the GABA(A) receptor was 67.4 mu M and that for the GABA(C) receptor was 1.9 mu M. These results sug gest that Zn2+ modulates the inhibitory interaction between amacrine and bi polar cells, particularly that mediated by the GABA(C) receptor.