Stimulation of glutamate receptors in cultured hippocampal neurons causes Ca2+-dependent mitochondrial contraction

Tatiana Brustovetsky, Viacheslav Li, Nickolay Brustovetsky

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Cultured hippocampal neurons expressing mitochondrially-targeted enhanced yellow fluorescent protein (mito-eYFP) were used to quantitatively examine mitochondrial remodelling in response to excitotoxic glutamate. Mitochondrial morphology was evaluated using laser spinning-disk confocal microscopy followed by calibrated image processing and 3D image rendering. Glutamate triggered an increase in cytosolic Ca2+ and mitochondrial depolarization accompanied by Ca2+-dependent morphological transformation of neuronal mitochondria from "thread-like" to rounded structures. The quantitative analysis of the mitochondrial remodelling revealed that exposure to glutamate resulted in a decrease in mitochondrial volume and surface area concurrent with an increase in sphericity of the organelles. NIM811, an inhibitor of the mitochondrial permeability transition, attenuated the glutamate-induced sustained increase in cytosolic Ca2+ and suppressed mitochondrial remodelling in the majority of affected neurons, but it did not rescue mitochondrial membrane potential. Shortening, fragmentation, and formation of circular mitochondria with decreased volume and surface area accompanied mitochondrial depolarization with FCCP. However, FCCP-induced morphological alterations appeared to be distinctly different from mitochondrial remodelling caused by glutamate. Moreover, FCCP prevented glutamate-induced mitochondrial remodelling suggesting an important role of Ca2+ influx into mitochondria in the morphological alterations. Consistent with this, in saponin-permeabilized neurons, Ca2+ caused mitochondrial remodelling which could be prevented by Ru360.

Original languageEnglish (US)
Pages (from-to)18-29
Number of pages12
JournalCell Calcium
Volume46
Issue number1
DOIs
StatePublished - Jul 2009

Keywords

  • Calcium
  • Confocal microscopy
  • Glutamate
  • Mitochondria
  • Neuron
  • Permeability transition

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

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