[The role of mitochondrial permeability transition pore in transmembrane Ca2+-exchange in mitochondria].
Ca2+-uptake accompanied with mitochondrial permeability transition pore (MPTP) opening is studied in rat liver mitochondria. In conditions of MPTP opening, as well as in conditions of MPTP blockage by cyclosporine A (CsA), Ca2+-uptake in mitochondria is counterbalanced by proton efflux into incubation medium. Independent of MPTP opening, observed stoichiometry of this exchange is 1Ca2+ : 1H+. MPTP opening dramatically decreases Ca2+-uptake in mitochondria: from approximately 400 nmol/mg protein in the presence of CsA to approximately 80-100 nmol/mg protein due to the increased mitochondrial membrane permeability. In the absence of CsA Ca2+-uptake is accompanied by the insensitive to Ca2+-uniporter blocker, ruthenium red (RR), release of Ca2+ from mitochondria which corresponds to as well RR-insensitive, but sensitive to CsA uptake of H+ into mitochondrial matrix. This calcium-proton exchange resulting from MPTP opening is observed only when Ca2+ uptake into matrix exceeds some basal level. The data are consistent with an assumption that, contrary to Ca2+-uniporter, MPTP has its own proton conductance. MPTP opening provides exchange of Ca2+ between mitochondria and medium which is coupled to the counterflow of protons into matrix space. Obtained data elucidate the physiological role of MPTP as regulatory mechanism for control of Ca2+-uptake level and intramitochondrial pH.
Akopova
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D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008930:Mitochondria, Liver / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D051381:Rats
D015220:Calcium Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; C034703:mitochondrial calcium uniporter; D016572:Cyclosporine; D002118:Calcium