Glutamate-induced calcium increase mediates magnesium release from mitochondria in rat hippocampal neurons

Yutaka Shindo, Ai Fujimoto, Kohji Hotta, Koji Suzuki, Kotaro Oka

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)


Excess administration of glutamate is known to induce Ca2+ overload in neurons, which is the first step in excitotoxicity. Although some reports have suggested a role for Mg2+ in the excitotoxicity, little is known about its actual contribution. To investigate the role of Mg2+ in the excitotoxicity, we simultaneously measured intracellular Ca2+ and Mg2+, using fluorescent dyes, Fura red, a fluorescent Ca2+ probe, and KMG-104, a highly selective fluorescent Mg2+ probe developed by our group, respectively. Administration of 100 μM glutamate supplemented with 10 μM glycine to rat hippocampal neurons induced an increase in intracellular Mg2+ concentration ([Mg2+]i). Extracellular Mg2+ was not required for this glutamate-induced increase in [Mg2+]i, and no increase in intracellular Ca2+ concentration ([Ca2+]i) or [Mg2+]i was observed in neurons in nominally Ca2+-free medium. Application of 5 μM carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP), an uncoupler of mitochondrial inner membrane potential, also elicited increases in [Ca2+]i and [Mg2+]i. Subsequent administration of glutamate and glycine following FCCP treatment did not induce a further increase in [Mg2+]i but did induce an additive increase in [Ca2+]i. Moreover, the glutamate-induced increase in [Mg2+]i was observed only in mitochondria localized areas. These results support the idea that glutamate is able to induced Mg2+ efflux from mitochondria to the cytosol. Furthermore, pretreatment with Ru360, an inhibitor of the mitochondrial Ca2+ uniporter, prevented this [Mg2+]i increase. These results indicate that glutamate-induced increases in [Mg2+]i result from the Mg2+ release from mitochondria and that Ca2+ accumulation in the mitochondria is required for this Mg2+ release.

Original languageEnglish
Pages (from-to)3125-3132
Number of pages8
JournalJournal of neuroscience research
Issue number14
Publication statusPublished - 2010 Nov 1


  • Excitotoxicity
  • Fluorescent imaging
  • Hippocampus
  • KMG-104
  • Mg

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience


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