Abstract
Inhibition of the mitochondrial KATP (mitoKATP) channel abrogates the beneficial effects of preconditioning induced by a brief episode of sublethal ischemia. We studied the effect of 5-hydroxydecanoate, a well-known inhibitor of the mitoKATP channel, on swelling of isolated liver and brain mitochondria. Volume changes were determined by measurement of light absorbance at 540 nm. Mitochondrial swelling induced by adding Ca2+ ions correlated with opening of the permeability transition pore as shown by modulation by 1 μM cyclosporin A. In brain mitochondria, 5-hydroxydecanoate did not significantly affect Ca2+-induced swelling. In contrast, 50 or 500 μM 5-hydroxydecanoate increased swelling of liver mitochondria by 9.7 ± 5.1% (n = 6, P = 0.057) and 29.4 ± 1.4% (n = 5, P < 0.0001), respectively. The effect of 5-hydroxydecanoate was blocked by cyclosporin A and was dependent on the presence of potassium in the medium. In medium containing 200 μM ATP to inhibit the mitoKATP channel, 5–hydroxydecanoate did not further increase Ca2+-induced swelling. We conclude that inhibition of the mitoKATP channel exerts its detrimental effect by facilitation of permeability transition pore opening.
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Kupsch, K., Parvez, S., Siemen, D. et al. Modulation of the Permeability Transition Pore by Inhibition of the Mitochondrial KATP Channel in Liver vs. Brain Mitochondria. J Membrane Biol 215, 69–74 (2007). https://doi.org/10.1007/s00232-007-9006-3
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DOI: https://doi.org/10.1007/s00232-007-9006-3