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. Zn(2+) at low concentration (<2 μM) potentiated the glycine-induced chloride current and at higher concentration (>10 μM) 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 μM Zn(2+) increased the maximum glycine response (I(∝)) and shifted the EC(50) to the left, suggesting that Zn(2+) at low concentrations acts as an allosteric activator of the strychnine-sensitive GlyRs. Zn(2+) at a concentration of 100 μM did not alter I(∝) and shifted the EC(50) to the right, indicating that Zn(2+) at high concentrations acts as a competitive inhibitor of the GlyRs. Physiological functions of zinc modulation of GlyRs in retinal ganglion cells are discussed.