Regulation of the mitochondrial permeability transition by matrix Ca(2+) and voltage during anoxia/reoxygenation.
We studied the interplay between matrix Ca(2+) concentration ([Ca(2+)]) and mitochondrial membrane potential (Deltapsi) in regulation of the mitochondrial permeability transition (MPT) during anoxia and reoxygenation. Without Ca(2+) loading, anoxia caused near-synchronous Deltapsi dissipation, mitochondrial Ca(2+) efflux, and matrix volume shrinkage when a critically low PO(2) was reached, which was rapidly reversible upon reoxygenation. These changes were related to electron transport inhibition, not MPT. Cyclosporin A-sensitive MPT did occur when extramitochondrial [Ca(2+)] was increased to promote significant Ca(2+) uptake during anoxia, depending on the Ca(2+) load size and ability to maintain Deltapsi. However, when [Ca(2+)] was increased after complete Deltapsi dissipation, MPT did not occur until reoxygenation, at which time reactivation of electron transport led to partial Deltapsi regeneration. In the setting of elevated extramitochondrial Ca(2+), this enhanced matrix Ca(2+) uptake while promoting MPT because of less than full recovery of Deltapsi. The interplay between Deltapsi and matrix [Ca(2+)] in accelerating or inhibiting MPT during anoxia/reoxygenation has implications for preventing reoxygenation injury associated with MPT.
Korge
P
P
Cardiovascular Research Laboratory, Department of Medicine, University of California at Los Angeles School of Medicine, Los Angeles, California 90095, USA.
Honda
H M
HM
Weiss
J N
JN
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D004594:Electrophysiology; D005109:Extracellular Matrix / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000502:physiology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010100:Oxygen / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D011817:Rabbits
D010100:Oxygen; D002118:Calcium