[Relese of Ca2+ from mitochondria after mitochondrial membrane depolarisation].
With the aid of specific inhibitors of Ca(2+)-uniporter (ruthenium red) and mitochondrial permeability transition pore, PTP (cyclosporine A) it is shown that PTP opening takes place after loading the rat liver mitochondria with calcium and depolarisation of mitochondrial membrane with protonophore (carbonyl cyanide m-chlorophenyl hydrazone, CCCP), and the pore opening accounts for accelerated efflux of calcium from mitochondrial matrix as well as availability of "rapid" component of two-exponential kinetic curve of Ca(2+)-efflux. An analysis of kinetic data of Ca2+ transport after membrane depolarisation also confirms our earlier observations that time frame of the pore open state is restricted, and membrane integrity is restored before all the calcium load is delivered into incubation medium. The absence of additivity between the shares of Ca(2+)-uniporter and PTP in Ca(2+)-transport is observed, and conclusion is made that partial share of PTP in calcium transport is not a constant, but a variable constituent which is diminished to zero as soon as the Ca(2+)-uniporter activity reaches its maximum after the abolition of membrane potential with CCCP. Based on some observations, it is supposed also that PTP inactivation takes place during calcium translocation across the mitochondrial membrane, which could account for limited release of Ca2+ from mitochondrial matrix through the pore itself as well as relatively narrow limits of the pore open state in comparison with time scale of complete cation release from depolarised mitochondria.
Akopova
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Sagach
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D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D010539:Permeability; D051381:Rats; D012430:Ruthenium Red / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; C034703:mitochondrial calcium uniporter; D012430:Ruthenium Red; D016572:Cyclosporine; D002118:Calcium