title: [Effect of Ca2+ on induction of the mitochondrial pore opening in the rat myocardium].
abstract: The mitochondrial role opening (MPT) induced by Ca2+ has been studied in isolated rat heart mitochondria. MPT was characterized as cyclosporine A-inhibited swelling accompanied by the loss of membrane potential (deltapsim) and Ca2+ efflux after the Ca2+ -loading which was followed spectrophotometrically after the Ca2+ -arsenaso-III complex formation. It has been shown that in suspension of isolated mitochondria MPT was activated by low (with maximum at about 20 microM Ca2+) and high concentrations of Ca2+ (the concentration curve shows a saturation at about 1.0-1.5 mM). In all the cases an access of Ca2+ ions to the matrix space of the mitochondria was necessary for MPT induction. MPT activated by low concentrations of Ca2+ was accompanied by slow decrease of deltapsim and slow release of Ca2+, enhanced by ruthenium red (RR), and was independent of the substrate used (glutamate or succinate). It had not been observed if the respiratory chain was inhibited, even if the Ca2+ access to the inner mitochondrial membrane was provided by Ca2+ -ionophore A23187. At high Ca2+ concentrations rapid Ca2+ -uptake and release via Ca2+ -uniporter (inhibited by ruthenium red) followed by extensive swelling (pore formation) have been observed. It had been supposed that rapid MPT at high concentrations of Ca2+ was the result of Ca2+ entrance to the mitochondrial matrix and depolarisation of the mitochondrial membrane. The data obtained show two different mechanisms of Ca2+ -induced MPT. The one is sensitive to the redox-state of the electron transport chain and is abolished if the respiration is inhibited. The other is independent of mitochondrial respiration and needs only Ca2+ access to the inner mitochondrial membrane and Ca2+ binding to some specific sites leading to MPT opening.
authors.forename: O V
authors.initials: OV
authors.lastname: Akopova
authors.forename: V F
authors.initials: VF
authors.lastname: Sagach
mesh_terms: D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000378:metabolism*; D007476:Ionophores / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000502:physiology; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009206:Myocardium / Q000378:metabolism*; D051381:Rats
chemical_list: D007473:Ion Channels; D007476:Ionophores; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D000001:Calcimycin; D002118:Calcium