2014•The Ukrainian Biochemical JournalOpen access

Activation of glybenclamide-sensitive mitochondrial swelling under induction of cyclosporin of A-sensitive mitochondrial pore

Olga B. Vadzyuk, Kosterin Sa

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Abstract

Induction of mitochondrial swelling and increased generation of reactive oxygen forms by Ca ions have been shown in suspension of mitochondria from rat uterus. These effects were suppressed by the blocker of mitochondrial Ca2+-uniporter ruthenium red and MPTP inhibitor cyclosporin A, that evidences that the induction of mitochondrial permeability transition pore by Ca ions takes place. Ca2+-induced mitochondrial swelling was blocked by ATP-sensitive channel blocker glybenclamide but only if K+ was present in the incubation medium. We also demonstrated that Ca2+-induced mitochondrial swelling can be eliminated in the presence of ROS scavengers N-acetyl cysteine and ascorbate. This effect of scavengers was also sensitive to K+ and was not revealed in the medium that contained equimolar NaCl instead of KCl. Thus, our data gave us grounds to assume that the induction of MPTP by Ca ions evokes the activation of mitochondrial ATPsensitive K+-channels, which are mediated by ROS.

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Induction of mitochondrial swelling and increased generation of reactive oxygen forms by Ca ions have been shown in suspension of mitochondria from rat uterus. These effects were suppressed by the blocker of mitochondrial Ca2+-uniporter ruthenium red and MPTP inhibitor cyclosporin A, that evidences that the induction of mitochondrial permeability transition pore by Ca ions takes place. Ca2+-induced mitochondrial swelling was blocked by ATP-sensitive channel blocker glybenclamide but only if K+ was present in the incubation medium. We also demonstrated that Ca2+-induced mitochondrial swelling can be eliminated in the presence of ROS scavengers N-acetyl cysteine and ascorbate. This effect of scavengers was also sensitive to K+ and was not revealed in the medium that contained equimolar NaCl instead of KCl. Thus, our data gave us grounds to assume that the induction of MPTP by Ca ions evokes the activation of mitochondrial ATPsensitive K+-channels, which are mediated by ROS.

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Available abstract

Induction of mitochondrial swelling and increased generation of reactive oxygen forms by Ca ions have been shown in suspension of mitochondria from rat uterus. These effects were suppressed by the blocker of mitochondrial Ca2+-uniporter ruthenium red and MPTP inhibitor cyclosporin A, that evidences that the induction of mitochondrial permeability transition pore by Ca ions takes place. Ca2+-induced mitochondrial swelling was blocked by ATP-sensitive channel blocker glybenclamide but only if K+ was present in the incubation medium. We also demonstrated that Ca2+-induced mitochondrial swelling can be eliminated in the presence of ROS scavengers N-acetyl cysteine and ascorbate. This effect of scavengers was also sensitive to K+ and was not revealed in the medium that contained equimolar NaCl instead of KCl. Thus, our data gave us grounds to assume that the induction of MPTP by Ca ions evokes the activation of mitochondrial ATPsensitive K+-channels, which are mediated by ROS.

Key concepts: Mitochondrial permeability transition pore, Ruthenium red, Uniporter, Chemistry, Mitochondrion, Biophysics, MPTP, Swelling

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Activation of glybenclamide-sensitive mitochondrial swelling under induction of cyclosporin of A-sensitive mitochondrial pore — Research Paper | ScholarLens