UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Excitotoxic mitochondrial depolarisation requires both calcium and nitric oxide in rat hippocampal neurons

Keelan, J; Vergun, O; Duchen, MR; (1999) Excitotoxic mitochondrial depolarisation requires both calcium and nitric oxide in rat hippocampal neurons. J PHYSIOL-LONDON , 520 (3) 797 - 813.

Full text not available from this repository.

Abstract

1. Glutamate neurotoxicity has been attributed to cellular Ca2+ overload. As mitochondrial depolarisation may represent a pivotal step in the progression to cell death, we have used digital imaging techniques to examine the relationship between cytosolic Ca2+ concentration ([Ca2+](c)) and mitochondrial potential (Delta Psi(m)) during glutamate toxicity, and to define the mechanisms underlying mitochondrial dysfunction.2. In cells of > 11 days in vitro (DIV), exposure to 50 mM potassium or 100 mu m glutamate had different consequences for Delta Psi(m). KCl caused a small transient loss of Delta Psi(m) but in response to glutamate there was a profound loss of Delta Psi(m). In cells of 7-10 DIV, glutamate caused only a modest and reversible drop in Delta Psi(m).3. Using fura-2 to measure [Ca2+](c), responses to KCl and glutamate did not appear significantly different. However, use of the low affinity indicator fura-2FF revealed a difference in the [Ca2+](c) responses to KCl and glutamate, which clearly correlated with the loss of Delta Psi(m). Neurons exhibiting a profound mitochondrial depolarisation also showed a large secondary increase in the fura-2FF ratio.4. The glutamate-induced loss of Delta Psi(m) was dependent on Ca2+ influx. However, inhibition of nitric oxide synthase (NOX) by L-NAME significantly attenuated the loss of Delta Psi(m). Furthermore, photolysis of caged NO at levels that had no effect alone promoted a profound mitochondrial depolarisation when combined with high [Ca2+](c), either in response to KCI or to glutamate in cultures at 7-10 DIV.5. In cells that showed only modest mitochondrial responses to glutamate, induction of a mitochondrial depolarisation by the addition of NO was followed by a secondary rise in [Ca2+](c). These data suggest that [Ca2+](c) and nitric oxide act synergistically to cause mitochondrial dysfunction and impaired [Ca2+](c) homeostasis during glutamate toxicity.

Type: Article
Title: Excitotoxic mitochondrial depolarisation requires both calcium and nitric oxide in rat hippocampal neurons
Keywords: METHYL-D-ASPARTATE, GLUTAMATE NEUROTOXICITY, MEDIATED NEUROTOXICITY, CELL-DEATH, DEVELOPMENTAL-CHANGES, GRANULE CELLS, SYNTHASE, OXYGEN, BRAIN, NMDA
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: http://discovery.ucl.ac.uk/id/eprint/120440
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item