Mitochondria consume energy and compromise cellular membrane potential by reversing ATP synthetase activity during focal ischemia in rats

Yoshimasa Takeda, Miguel A. Pérez-Pinzón, Myron D. Ginsberg, Thomas J. Sick

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Abstract

The direction of the chemical reaction of ATP synthetase is reversible. The present study was designed to determine whether mitochondria produce or consume ATP during ischemia. For this purpose, changes in mitochondria membrane potential were measured in vivo at the site of a direct current (DC) electrode using a potentiometric dye, 5,5′,6,6′-tetrachloro-1,1′,3, 3′-tetraethylbenzimidazolylcarbocyanine iodide (JC-1), and a rat model of focal ischemia. Two μL of dye (control group) or dye with oligomycin, an ATP synthetase inhibitor (oligomycin group), was injected into the parietotemporal cortex through the DC electrode. With the initiation of ischemia, a decrease in mitochondrial potential was observed within 20 seconds in the oligomycin group (earlier than the onset of DC deflection, P = 0.02). In contrast, in the control group, mitochondrial potential was maintained at 91 ± 5% of the pre-ischemia level for 118 ± 38 seconds before showing full depolarization simultaneously with DC deflection. During the period of ischemia, the mitochondrial potential was higher in the control group (66 ± 9%) than in the oligomycin group (46 ± 8%, P = 0.0002), whereas DC potential was lower in the control group (-18 ± 3) than in the oligomycin group (-15 ± 2 mV, P = 0.04). These observations suggest that mitochondria consume ATP during ischemia by reversing ATP synthetase activity, which compromises cellular membrane potential by consuming ATP.

Original languageEnglish
Pages (from-to)986-992
Number of pages7
JournalJournal of Cerebral Blood Flow and Metabolism
Volume24
Issue number9
DOIs
Publication statusPublished - Sep 2004

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Keywords

  • Brain ischemia
  • DC potential
  • Membrane depolarization
  • Mitochondrial potential
  • Neuronal damage
  • Preconditioning

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

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