Zinc selectively blocks the action of N-methyl-D-aspartate on cortical neurons.
Large amounts of zinc are present in synaptic vesicles of mammalian central excitatory boutons and may be released during synaptic activity, but the functional significance of the metal for excitatory neurotransmission is currently unknown. Zinc (10 to 1000 micromolar) was found to have little intrinsic membrane effect on cortical neurons, but invariably produced a zinc concentration-dependent, rapid-onset, reversible, and selective attenuation of the membrane responses to N-methyl-D-aspartate, homocysteate, or quinolinate. In contrast, zinc generally potentiated the membrane responses to quisqualate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and often did not affect the response to kainate. Zinc also attenuated N-methyl-D-aspartate receptor-mediated neurotoxicity but not quisqualate or kainate neurotoxicity. The ability of zinc to specifically modulate postsynaptic neuronal responses to excitatory amino acid transmitters, reducing N-methyl-to-aspartate receptor-mediated excitation while often increasing quisqualate receptor-mediated excitation, is proposed to underlie its normal function at central excitatory synapses and furthermore could be relevant to neuronal cell loss in certain disease states.
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002462:Cell Membrane / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology*; D004347:Drug Interactions; D004594:Electrophysiology; D006710:Homocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D016202:N-Methylaspartate; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010069:Oxadiazoles / Q000494:pharmacology; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000494:pharmacology; D016318:Quisqualic Acid; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology; D015032:Zinc / Q000494:pharmacology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D010069:Oxadiazoles; D011805:Quinolinic Acids; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D006710:Homocysteine; C007956:homocysteic acid; D007051:Ibotenic Acid; D001224:Aspartic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid; D017378:Quinolinic Acid; D008274:Magnesium; D015032:Zinc; D007608:Kainic Acid