Acidification reduces mitochondrial calcium uptake in rat cardiac mitochondria

Hema I. Gursahani, Saul Schaefer

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39 Scopus citations

Abstract

Cardiac ischemia-reperfusion (I/R) injury is accompanied by intracellular acidification that can lead to cytosolic and mitochondrial calcium overload. However, the effect of cytosolic acidification on mitochondrial pH (pH m) and mitochondrial Ca2+ (Cam 2+) handling is not well understood. In the present study, we tested the hypothesis that changes in pHm during cytosolic acidification can modulate Cam 2+ handling in cardiac mitochondria. pHm was measured in permeabilized rat ventricular myocytes with the use of confocal microscopy and the pH-sensitive fluorescent probe carboxyseminaphthorhodafluor- 1. The contributions of the mitochondrial Na+/H+ exchanger (NHEm) and the K+/H+ exchanger (KHE m) to pHm regulation were evaluated using acidification and recovery protocols to mimic the changes in pH observed during I/R. Ca m 2+ transport in isolated mitochondria was measured using spectrophotometry and fluorimetry, and the mitochondrial membrane potential was measured using a tetraphenylphosphonium electrode. Cytosolic acidification (pH 6.8) resulted in acidification of mitochondria. The degree of mitochondrial acidification and recovery was found to be largely dependent on the activity of the KHEm. However, the NHEm was observed to contribute to the recovery of pHm following acidification in K+-free solutions as well as the maintenance of pHm during respiratory inhibition. Acidification resulted in mitochondrial depolarization and a decrease in the rate of net Cam 2+ uptake, whereas restoration of pH following acidification increased Cam 2+ uptake. These findings are consistent with an important role for cytosolic acidification in determining pHm and Cam 2+ handling in cardiac mitochondria under conditions of Ca2+ overload. Consequently, interventions that alter pHm can limit Ca m 2+ overload and injury during I/R.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume287
Issue number6 56-6
DOIs
StatePublished - Dec 2004

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Keywords

  • Mitochondrial calcium
  • Mitochondrial membrane potential
  • Mitochondrial pH
  • Potassium/hydrogen exchange
  • Sodium/hydrogen exchange

ASJC Scopus subject areas

  • Physiology

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