Intramitochondrial [Ca21] and membrane potential in ventricular myocytes exposed to anoxia-reoxygenation

Delcamp, T. J., C. Dales, L. Ralenkotter, P. S. Cole, and R. W. Hadley. Intramitochondrial [Ca21] and membrane potential in ventricular myocytes exposed to anoxia-reoxygenation. Am. J. Physiol. 275 (Heart Circ. Physiol. 44): H484– H494, 1998.—The aim of this study was to investigate the role of mitochondrial ionic homeostasis in promoting reoxygenation-induced hypercontracture in cardiac muscle. Mitochondrial membrane potential and intramitochondrial Ca21 concentration ([Ca21]) were measured using confocal imaging in guinea pig ventricular myocytes exposed to anoxia and reoxygenation. Anoxia produced a variable, but often profound, mitochondrial depolarization. Some cells mounted a recovery of their mitochondrial membrane potential during reoxygenation; the depolarization was sustained in other cells. Recovery of the mitochondrial membrane potential seemed essential to avoid reoxygenation-induced hypercontracture. Reoxygenation also caused a sizable elevation in intramitochondrial [Ca21], the amplitude of which was correlated with the likelihood of a cell undergoing hypercontracture. A sustained Ca21 load analogous to that seen during reoxygenation was imposed on cardiac mitochondria through permeabilization of the plasma membrane. Elevation of intracellular [Ca21] to 800 nM caused a substantial mitochondrial depolarization. We propose that the conditions seen in guinea pig ventricular myocytes during reoxygenation are well suited to produce Ca21-dependent mitochondrial depolarization, which may play a significant role in promoting irreversible cell injury.