Modulation of glycine receptors in retinal ganglion cells by zinc.

Effects of zinc, an endogenous neuromodulator in the central nervous system, on glycine receptors (GlyRs) in retinal ganglion cells were investigated by using the whole-cell voltage-clamp technique. Zn2+ at low concentration (<2 microM) potentiated the glycine-induced chloride current and at higher concentration (>10 microM) suppressed it. This biphasic regulatory action of zinc acted selectively on the fast component of the glycine-induced current mediated by the strychnine-sensitive GlyRs, but not on the slow component mediated by the 5,7-dichlorokynurenic acid-sensitive GlyRs. Dose-response studies showed that 1 microM Zn2+ increased the maximum glycine response (I approximately) and shifted the EC50 to the left, suggesting that Zn2+ at low concentrations acts as an allosteric activator of the strychnine-sensitive GlyRs. Zn2+ at a concentration of 100 microM did not alter I approximately and shifted the EC50 to the right, indicating that Zn2+ at high concentrations acts as a competitive inhibitor of the GlyRs. Physiological functions of zinc modulation of GlyRs in retinal ganglion cells are discussed.