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Potentiation of 45 Ca Uptake and Acute Toxicity Mediated by the N ‐Methyl‐D‐Aspartate Receptor: The Effect of Metal Binding Agents and Transition Metal Ions
Author(s) -
Eimerl Sara,
Schramm Michael
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb02154.x
Subject(s) - nmda receptor , chemistry , neurotoxicity , long term potentiation , receptor , metal , toxicity , calcium , biophysics , biochemistry , biology , organic chemistry
The activities mediated by the N ‐methyl‐D‐aspartate (NMDA) receptor were studied in cultured rat cerebellar granule cells. Micromolar concentrations of the metal binding compounds, EDTA, cysteine, and histidine, as well as serum albumin strongly potentiated receptor activity in the presence of millimolar concentrations of Ca 2+ and Mg 2+ . The findings indicated that these agents remove an endogenous metal, probably Zn 2+ , which attenuates NMDA receptor‐mediated 45 Ca uptake and toxicity. Several added metal ions were therefore tested at low micromolar concentrations. Zn 2+ was found to be the most potent inhibitor of NMDA‐induced 45 Ca uptake, followed by Cu 2+ and Fe 2+ . Co 2+ , Cd 2+ , Fe 3+ , and AI 3+ had no significant effect, whereas Ni 2+ potentiated the 45 Ca uptake but inhibited at much higher concentrations. The potentiating agents that remove the endogenous metal had a particularly dramatic effect in the presence of Mg 2+ , the voltage‐dependent suppressor of the NMDA receptor. Mg 2+ also played an important role in the inhibitory effect of added Zn 2+ . Much lower concentrations of Zn 2+ were needed to achieve inhibition of NMDA‐induced 45 Ca uptake in the presence of Mg 2+ . Under a variety of conditions, a very good correlation was found between NMDA receptor‐mediated 45 Ca uptake and the magnitude of acute neurotoxicity.