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NMDA Receptor‐Mediated Neurotoxicity: A Paradoxical Requirement for Extracellular Mg 2+ in Na + /Ca 2+ ‐Free Solutions in Rat Cortical Neurons In Vitro
Author(s) -
Hartnett K. A.,
Stout A. K.,
Rajdev S.,
Rosenberg P. A.,
Reynolds I. J.,
Aizenman E.
Publication year - 1997
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 - 10.1046/j.1471-4159.1997.68051836.x
Subject(s) - nmda receptor , excitotoxicity , neurotoxicity , glutamate receptor , extracellular , intracellular , agonist , chemistry , biophysics , receptor , biochemistry , biology , toxicity , organic chemistry
Accumulation of intracellular Ca 2+ is known to be critically important for the expression of NMDA receptor‐mediated glutamate neurotoxicity. We have observed, however, that glutamate can also increase the neuronal intracellular Mg 2+ concentration on activation of NMDA receptors. Here, we used conditions that elevate intracellular Mg 2+ content independently of Ca 2+ to investigate the potential role of Mg 2+ in excitotoxicity in rat cortical neurons in vitro. In Ca 2+ ‐free solutions in which the Na + was replaced by N ‐methyl‐ d ‐glucamine or Tris (but not choline), which also contained 9 m M Mg 2+ , exposure to 100 µ M glutamate or 200 µ M NMDA for 20 min produced delayed neuronal cell death. Neurotoxicity was correlated to the extracellular Mg 2+ concentration and could be blocked by addition of NMDA receptor antagonists during, but not immediately following, agonist exposure. Finally, we observed that rat cortical neurons grown under different serum conditions develop an altered sensitivity to Mg 2+ ‐dependent NMDA receptor‐mediated toxicity. Thus, the increase in intracellular Mg 2+ concentration following NMDA receptor stimulation may be an underestimated component critical for the expression of certain forms of excitotoxic injury.