Neuroprotective effect of KB-r7943 against glutamate excitotoxicity is related to mild mitochondrial depolarization

T. P. Storozhevykh, Ya E. Senilova, T. Brustovetsky, V. G. Pinelis, N. Brustovetsky

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

KB-R7943, an inhibitor of a reversed Na+/Ca2+ exchanger, exhibits neuroprotection against glutamate excitotoxicity. Taking into consideration that prolonged exposure of neurons to glutamate induces delayed calcium deregulation (DCD) and irreversible decrease of mitochondrial membrane potential (Δψmit), we examined the effect of KB-R7943 on glutamate and kainate-induced [Ca2+]i and on Δψmit changes in rat cultured cerebellar granule neurons. 15 μmol/l KB-R7943 significantly delayed the onset of DCD in response to kainate but not in response to glutamate. In spite of [Ca2+] i overload, KB-R7943 considerably improved the [Ca2+] i recovery and restoration of Δψmit after glutamate and kainate washout and increased cell viability after glutamate exposure. In resting neurons, KB-R7943 induced a statistically significant decrease in Δψmit. KB-R7943 also depolarized isolated brain mitochondria and slightly inhibited mitochondrial Ca2+ uptake. These findings suggest that mild mitochondrial depolarization and diminution of Ca2+ accumulation in the organelles might contribute to neuroprotective effect of KB-R7943.

Original languageEnglish (US)
Pages (from-to)323-335
Number of pages13
JournalNeurochemical Research
Volume35
Issue number2
DOIs
StatePublished - Feb 1 2010

Keywords

  • Delayed calcium deregulation
  • KB-R7943
  • Mitochondria
  • Na/Ca exchanger
  • Neuron

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Biochemistry

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