Increased permeability of mitochondria during Ca2+ release induced by t-butyl hydroperoxide or oxalacetate. the effect of ruthenium red.
Ca2+ release from mitochondria induced by oxalacetate or t-butyl hydroperoxide is accompanied by loss of endogenous Mg2+ and K+, swelling, loss of membrane potential, and other alterations which indicate that Ca2+ release is a result of increased inner membrane permeability. When ruthenium red is added after Ca2+ uptake, but before the releasing agent, the extent of Ca2+ release is diminished as is the extent of Mg2+ and K+ depletion and the extent of swelling. Under these conditions, the membrane potential appears to remain at a high value. When Ca2+ release is induced by oxalacetate or t-butyl hydroperoxide and ruthenium red is added subsequently, an apparent regeneration of membrane potential is observed providing that the associated swelling and Mg2+ loss had not been completed at the time ruthenium red was added. Under these conditions subsequent swelling and Mg2+ loss are inhibited.l Ultrastructural observations show the mitochondria become permeable in response to Ca2+ plus oxalacetate or Ca2+ plus t-butyl hydroperoxide in a heterogeneous manner. Conditions which appear to separate Ca2+ release from a decline in membrane potential or to produce an apparent recovery of membrane potential following partial collapse are shown to prevent a subpopulation of the mitochondria from becoming permeable. It is shown that membrane potential probes will not indicate a decline in potential or the presence of a permeable fraction under these conditions. It is concluded that the presence of Ca2+ accumulation inhibitors does not separate Ca2+ release from the development of increased inner membrane permeability.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003992:Dibucaine / Q000494:pharmacology; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010071:Oxaloacetates / Q000494:pharmacology*; D010539:Permeability; D010545:Peroxides / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012428:Ruthenium / Q000494:pharmacology*; D012430:Ruthenium Red / Q000494:pharmacology*; D020122:tert-Butylhydroperoxide
D010071:Oxaloacetates; D010545:Peroxides; D012430:Ruthenium Red; D012428:Ruthenium; D020122:tert-Butylhydroperoxide; D008274:Magnesium; D003992:Dibucaine; D011188:Potassium; D002118:Calcium