[Low concentrations of cyclosporin A close Ca2+-dependent inner mitochondrial membrane pores in the absence of other effectors].
Earlier it has been demonstrated that the recoupling action of cyclosporin A on mitochondria deenergized by the opening of the Ca(+)-dependent pore requires higher cyclosporin A concentrations than those, which are necessary for preventing the permeabilization as well as the presence of additional effectors, such as adenine nucleotides and Mg2+. It has been shown that cyclosporin A reseals the pore and prevents its opening when used at the same low concentrations (0.1-0.4 microM), while its higher concentrations (0.5-1.0 microM) produce the recoupling of mitochondria. In contrast with recoupling, resealing of the pore by cyclosporin A does not require Mg2+ or adenine nucleotides. Carboxyatractylate which reverses the cyclosporin A-induced restoration of the membrane potential does not induce repeated opening of the pore. The carboxyatractylate-induced depolarization of the inner mitochondrial membrane is sensitive to ruthenium red. Besides, ruthenium red restores the recoupling action of cyclosporin A in the absence of carboxyatractylate. The data obtained suggest that the loss by cyclosporin A of its recoupling potency may result from the induction of the Ca2+/2H+ antiporter. Induction of the Ca2+/2H+ antiporter in combination with a ruthenium red-sensitive Ca2+ uniporter provides the uncoupling mitochondria even with a closed Ca(2+)-dependent pore. Apparently, Ca2+/2H+ antiporter induction is a result of inhibition of the ADP/ATP antiporter by a natural or exogenous inhibitor. This process seems to require a preliminary release of certain protective factors from the mitochondrial matrix.
Kushnareva
Iu E
IuE
Mikhaĭlova
L M
LM
Andreev
A Iu
AIu
D000227:Adenine Nucleotides / Q000494:pharmacology; D000818:Animals; D017920:Antiporters / Q000096:biosynthesis; D001278:Atractyloside / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis; D027682:Cation Transport Proteins; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000187:drug effects* / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D012430:Ruthenium Red / Q000494:pharmacology
D000227:Adenine Nucleotides; D017920:Antiporters; D002135:Calcium-Binding Proteins; D027682:Cation Transport Proteins; C027614:calcium-hydrogen antiporters; D012430:Ruthenium Red; D001278:Atractyloside; D016572:Cyclosporine; D008274:Magnesium; C003853:carboxyatractyloside; D002118:Calcium
Nizkie kontsentratsii tsiklosporina A zakryvaiut Ca2+-zavisimuiu poru vnutrenneĭ membrany mitokhondriĭ v otsutstvie dopolnitel'nykh éffektorov.