Effect of cyclosporin A on isolated mitochondria from normal and ischemic rat brain |
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| Authors: | WU Li-ping SHEN Fang LIN Lin LU Yuan XIA QiangWU Li-ping SHEN Fang LIN Lin LU Yuan XIA Qiang |
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| Institution: | Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310031, China. E-mail: xiaqiang@zju.edu.cn |
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| Abstract: | AIM: The purpose of this study was to investigate the effect of cyclosporin A on the isolated mitochondria from normal and ischemic rat brains and to observe the possible effect of mitochondrial ATP sensitive potassium channel on mitochondrial permeability transition. METHODS: The swelling of mitochondria isolated from normal and ischemic rat brain was evaluated by pectrophotometry. RESULTS: Cyclosporin A at concentrations of 0.5 μmol/L or 1 μmol/L and diazoxide at concentration of 30 μmol/L significantly decreased the swelling of the normal brain mitochondria induced by 200 μmol/L calcium, which was abolished by atractyloside at 100 μmol/L. However, cyclosporin A at concentration of 5 μmol/L did not affect the mitochondrial swelling. On the mitochondria isolated from ischemic brain, cyclosporin A at 0.5 μmol/L but not 1 μmol/L significantly decreased the mitochondrial swelling, which was cancelled by atractyloside at concentration of 100 μmol/L. Diazoxide at concentration of 30 mol/L had the similar effect with cyclosporin A at 0.5 μmol/L, which was locked by atractyloside at 100 μmol/L or 5-hydroxydecanoate at 100 μmol/L and 200 μmol/L. CONCLUSIONS: Compared with the mitochondria isolated from normal brain, mitochondria from ischemic brain are more sensitive to the inhibition of mitochondria permeability transition pore opening. Activation of mitochondrial ATP potassium channel may be one of the mechanisms by which the opening of mitochondrial permeability transition pore is inhibited. |
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| Keywords: | Mitochondrial permeability transition pore Potassium channels ATP sensitive Brain ischemia Cyclosporine |
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