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 microM) and potentiated both AMPA (EC50 = 30.0 +/- 1.2 microM) and desensitized kainate responses (EC50 = 13.0 +/- 0.1 microM). 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 microM Zn2+ differentially affected NMDA and non-NMDA components of the glutamate-induced response. The possible physiological relevance of Zn2+ modulation is discussed.
Rassendren
F A
FA
CNRS UPR 8402, INSERM U249, Université Montpellier I, France.
Lory
P
P
Pin
J P
JP
Nargeot
J
J
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity / Q000187:drug effects / Q000502:physiology; D005260:Female; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D009865:Oocytes / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure*; D018091:Receptors, AMPA; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000502:physiology; D014982:Xenopus laevis / Q000502:physiology*; D015032:Zinc / Q000494:pharmacology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D007051:Ibotenic Acid; D018091:Receptors, AMPA; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D015032:Zinc; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid