INTRAMITOCHONDRIAL [CA2-POTENTIAL IN VENTRICULAR MYOCYTES EXPOSED TO ANOXIA-REOXYGENATION(] AND MEMBRANE)

The aim of this study was to investigate the role of mitochondrial ion ic homeostasis in promoting reoxygenation-induced hypercontracture in cardiac muscle. Mitochondrial membrane potential and intramitochondria l Ca2+ concentration ([Ca2+]) were measured using confocal imaging in guinea pig ventricular myocytes exposed to anoxia and reoxygenation. A noxia produced a variable, but often profound, mitochondrial depolariz ation. Some cells mounted a recovery of their mitochondrial membrane p otential during reoxygenation; the depolarization was sustained in oth er cells. Recovery of the mitochondrial membrane potential seemed esse ntial to avoid reoxygenation-induced hypercontracture. Reoxygenation a lso caused a sizable elevation in intramitochondrial [Ca2+], the ampli tude of which was correlated with the likelihood of a cell undergoing hypercontracture. A sustained Ca2+ load analogous to that seen during reoxygenation was imposed on cardiac mitochondria through permeabiliza tion of the plasma membrane. Elevation of intracellular [Ca2+] to 800 nM caused a substantial mitochondrial depolarization. We propose that the conditions seen in guinea pig ventricular myocytes during reoxygen ation are well suited to produce Ca2+-dependent mitochondrial depolari zation, which may play a significant role in promoting irreversible ce ll injury.