Glutamate‐Induced Loss of Ca2+/Calmodulin‐Dependent Protein Kinase II Activity in Cultured Rat Hippocampal Neurons

Motohiro Morioka, Kohji Fukunaga, Shinji Nagahiro, Masahito Kurino, Yukitaka Ushio, Eishichi Miyamoto

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Abstract: The exposure of cultured rat hippocampal neurons to 500 µM glutamate for 20 min induced a 55% decrease in the total Ca2+/calmodulin‐dependent protein kinase II (CaM kinase II) activity. The Ca2+‐independent activity and autophosphorylation of CaM kinase II decreased to the same extent as the changes observed in total CaM kinase II activity, and these decreases in activities were prevented by pretreatment with MK‐801, an N‐methyl‐d‐aspartate (NMDA)‐type receptor antagonist, and the removal of extracellular calcium but not by antagonists against other types of glutamate receptors and protease inhibitors. Similarly, the decrease in the CaM kinase II activity was induced by a Ca2+ ionophore, ionomycin. Immunoblot analysis with the anti‐CaM kinase II antibody revealed a significant decrease in the amount of the enzyme in the soluble fraction, in contrast with the inverse increase in the insoluble fraction; thus, the translocation was probably induced during treatment of the cells with glutamate. These results suggest that glutamate released during brain ischemia induces a loss of CaM kinase II activity in hippocampal neurons, by stimulation of the NMDA receptor, and that inactivation of the enzyme may possibly be involved in the cascade of the glutamate neurotoxicity following brain ischemia.

Original languageEnglish
Pages (from-to)2132-2139
Number of pages8
JournalJournal of Neurochemistry
Volume64
Issue number5
DOIs
Publication statusPublished - 1995 May
Externally publishedYes

Keywords

  • Brain ischemia
  • Ca/calmodulin‐dependent protein kinase II
  • Glutamate neurotoxicity
  • Hippocampus
  • NMDA receptor

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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