Glutamate-induced neuron death requires mitochondrial calcium uptake

Amy K. Stout, Heather M. Raphael, Beatriz I. Kanterewicz, Eric Klann, Ian J. Reynolds

Research output: Contribution to journalArticlepeer-review


We have investigated the role of mitochondrial calcium buffering in excitotoxic cell death. Glutamate acts at NMDA receptors in cultured rat forebrain neurons to increase the intracellular free calcium concentration. Although concurrent inhibition of mitochondrial calcium uptake substantially enhanced this cytoplasmic calcium increase, it significantly reduced glutamate-stimulated neuronal cell death. Mitochondrial inhibition did not affect nitric oxide production or MAP kinase phosphorylation, which have been proposed to mediate excitotoxicity. These results indicate that very high levels of cytoplasmic calcium are not necessarily toxic to forebrain neurons, and that potential-driven uptake of calcium into mitochondria is required to trigger NMDA-receptor-stimulated neuronal death.

Original languageEnglish (US)
Pages (from-to)366-373
Number of pages8
JournalNature Neuroscience
Issue number5
StatePublished - 1998

ASJC Scopus subject areas

  • General Neuroscience


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