ZINC HAS OPPOSITE EFFECTS ON NMDA AND NON-NMDA RECEPTORS EXPRESSED IN XENOPUS OOCYTES

Pharmacological characterization of Zn2+ effects on glutamate ionotropic receptors was investigated in Xenopus oocytes injected with rat brain mRNA, using a double microelectrode, voltage-clamp technique. At low concentration, Zn2+ inhibited NMDA currents (IC50 = 42.9 ± 1.3 μM) and potentiated both AMPA (EC50 = 30.0 ± 1.2 μM) and desensitized kainate responses (EC50 = 13.0 ± 0.1 μM). At higher concentrations, Zn2+ inhibited non-NMDA responses with IC50 values of 1.3 ± 0.1 mM and 1.2 ± 0.3 mM for AMPA and kainate, respectively. The potentiation of AMPA or quisqualate currents by Zn2+ was more than 2-fold, whereas that of the kainate current was only close to 30%. This potentiating effect of Zn2+ on AMPA current modified neither the affinity of the agonist for its site nor the current-voltage relationship. In addition, 500 μM Zn2+ differentially affected NMDA and non-NMDA components of the glutamate-induced response. The possible physiological relevance of Zn2+ modulation is discussed. © 1990.