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

Abstract

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 μM bicuculline, suggesting that this is a GABA_A-receptor mediated current. The second component was inhibited completely by 100 μM 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 μM and that for the GABA_C receptor was 1.9 μM. These results suggest that Zn²⁺ modulates the inhibitory interaction between amacrine and bipolar cells, particularly that mediated by the GABA_C receptor.