Intramitochondrial [Ca2+] and membrane potential in ventricular myocytes exposed to anoxia-reoxygenation.
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 Ca2+ concentration ([Ca2+]) 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 [Ca2+], the amplitude 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 permeabilization 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 reoxygenation are well suited to produce Ca2+-dependent mitochondrial depolarization, which may play a significant role in promoting irreversible cell injury.
Department of Pharmacology, College of Medicine, University of Kentucky, Lexington, Kentucky 40536-0084, USA.
T J
TJ
Delcamp
C
C
Dales
L
L
Ralenkotter
P S
PS
Cole
R W
RW
Hadley
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015687:Cell Hypoxia; D002463:Cell Membrane Permeability; D002467:Cell Nucleus / Q000502:physiology; D002478:Cells, Cultured; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D007425:Intracellular Membranes / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials; D018613:Microscopy, Confocal; D008929:Mitochondria, Heart / Q000502:physiology*; D009685:Nuclear Envelope / Q000502:physiology; D010100:Oxygen; D013997:Time Factors
D010100:Oxygen; D002118:Calcium