Measurements of mitochondrial pH in cultured cortical neurons clarify contribution of mitochondrial pore to the mechanism of glutamate-induced delayed Ca2+ deregulation

Alexey P. Bolshakov, Maria M. Mikhailova, György Szabadkai, Vsevolod G. Pinelis, Nikolai Broustovetski, Rosario Rizzuto, Boris I. Khodorov

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Abstract

To clarify the role of the mitochondrial permeability transition pore (MPT) in the mechanism of the glutamate-induced delayed calcium deregulation (DCD) and mitochondrial depolarization (MD), we studied changes in cytosolic (pHc) and mitochondrial pH (pHm) induced by glutamate in cultured cortical neurons expressing pH-sensitive fluorescent proteins. We found that DCD and MD were associated with a prominent pHm decrease which presumably resulted from MPT opening. This pHm decrease occurred with some delay after the onset of DCD and MD. This argued against the hypothesis that MPT opening plays a dominant role in triggering of DCD. This conclusion was also supported by experiments in which Ca2+ was replaced with antagonist of MPT opening Sr2+. We found that in Sr2+-containing medium glutamate-induced delayed strontium deregulation (DSD), similar to DCD, which was accompanied by a profound MD. Analysis of the changes in pHc and pHm associated with DSD led us to conclude that MD in Sr2+-containing medium occurred without involvement of the pore. In contrast, in Ca2+-containing medium such "non-pore mechanism" was responsible only for MD initiation while in the final stages of MD development the MPT played a major role.

Original languageEnglish
Pages (from-to)602-614
Number of pages13
JournalCell Calcium
Volume43
Issue number6
DOIs
StatePublished - Jun 2008

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Glutamic Acid
Calcium
Neurons
Strontium
mitochondrial permeability transition pore
Proteins

Keywords

  • Calcium deregulation
  • Excitotoxicity
  • Glutamate
  • Mitochondria
  • Mitochondrial permeability transition

ASJC Scopus subject areas

  • Cell Biology
  • Endocrinology

Cite this

Measurements of mitochondrial pH in cultured cortical neurons clarify contribution of mitochondrial pore to the mechanism of glutamate-induced delayed Ca2+ deregulation. / Bolshakov, Alexey P.; Mikhailova, Maria M.; Szabadkai, György; Pinelis, Vsevolod G.; Broustovetski, Nikolai; Rizzuto, Rosario; Khodorov, Boris I.

In: Cell Calcium, Vol. 43, No. 6, 06.2008, p. 602-614.

Research output: Contribution to journalArticle

Bolshakov, Alexey P. ; Mikhailova, Maria M. ; Szabadkai, György ; Pinelis, Vsevolod G. ; Broustovetski, Nikolai ; Rizzuto, Rosario ; Khodorov, Boris I. / Measurements of mitochondrial pH in cultured cortical neurons clarify contribution of mitochondrial pore to the mechanism of glutamate-induced delayed Ca2+ deregulation. In: Cell Calcium. 2008 ; Vol. 43, No. 6. pp. 602-614.
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AU - Pinelis, Vsevolod G.

AU - Broustovetski, Nikolai

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