Korotkov Sergey M, Brailovskaya Irina V, Shumakov Anton R, Emelyanova Larisa V
Sechenov Institute of Evolutionary Physiology and Biochemistry, The Russian Academy of Sciences, Thorez pr. 44, 194223, St. Petersburg, Russia,
J Bioenerg Biomembr. 2015 Jun;47(3):243-54. doi: 10.1007/s10863-015-9611-2. Epub 2015 Apr 14.
It is known that a closure of ATP sensitive (mitoKATP) or BK-type Ca(2+) activated (mitoKCa) potassium channels triggers opening of the mitochondrial permeability transition pore (MPTP) in cells and isolated mitochondria. We found earlier that the Tl(+)-induced MPTP opening in Ca(2+)-loaded rat liver mitochondria was accompanied by a decrease of 2,4-dinitrophenol-uncoupled respiration and increase of mitochondrial swelling and ΔΨmito dissipation in the medium containing TlNO3 and KNO3. On the other hand, our study showed that the mitoKATP inhibitor, 5-hydroxydecanoate favored the Tl(+)-induced MPTP opening in the inner membrane of Ca(2+)-loaded rat heart mitochondria (Korotkov et al. 2013). Here we showed that 5-hydroxydecanoate increased the Tl(+)-induced MPTP opening in the membrane of rat liver mitochondria regardless of the presence of mitoKATP modulators (diazoxide and pinacidil). This manifested in more pronounced decrease in the uncoupled respiration and acceleration of both the swelling and the ΔΨmito dissipation in isolated rat liver mitochondria, incubated in the medium containing TlNO3, KNO3, and Ca(2+). A slight delay in Ca(2+)-induced swelling of the mitochondria exposed to diazoxide could be result of an inhibition of succinate oxidation by the mitoKATP modulator. Mitochondrial calcium retention capacity (CRC) was markedly decreased in the presence of the mitoKATP inhibitor (5-hydroxydecanoate) or the mitoKCa inhibitor (paxilline). We suggest that the closure of mitoKATP or mitoKCa in calcium loaded mitochondria favors opening of the Tl(+)-induced MPTP in the inner mitochondrial membrane.
已知ATP敏感性（线粒体ATP敏感性钾通道，mitoKATP）或BK型钙激活（线粒体钙激活钾通道，mitoKCa）钾通道的关闭会触发细胞和分离线粒体中，线粒体通透性转换孔（MPTP）的开放。我们之前发现，在钙离子负载的大鼠肝线粒体中，铊离子（Tl⁺）诱导的MPTP开放伴随着2,4-二硝基苯酚解偶联呼吸的降低，以及在含有硝酸铊（TlNO₃）和硝酸钾（KNO₃）的培养基中线粒体肿胀和线粒体膜电位（ΔΨmito）耗散的增加。另一方面，我们的研究表明，mitoKATP抑制剂5-羟基癸酸有利于在钙离子负载的大鼠心脏线粒体内膜中，铊离子（Tl⁺）诱导的MPTP开放（科罗特科夫等人，2013年）。在这里我们表明，无论是否存在mitoKATP调节剂（二氮嗪和匹那地尔），5-羟基癸酸都会增加大鼠肝线粒体膜中铊离子（Tl⁺）诱导的MPTP开放。这表现为在含有硝酸铊（TlNO₃）、硝酸钾（KNO₃）和钙离子（Ca²⁺）的培养基中孵育的分离大鼠肝线粒体中，解偶联呼吸更明显的降低，以及肿胀和线粒体膜电位（ΔΨmito）耗散的加速。暴露于二氮嗪的线粒体中，钙离子诱导的肿胀略有延迟，可能是mitoKATP调节剂抑制琥珀酸氧化的结果。在存在mitoKATP抑制剂（5-羟基癸酸）或mitoKCa抑制剂（鬼笔环肽）的情况下，线粒体钙保留能力（CRC）显著降低。我们认为，钙离子负载的线粒体中mitoKATP或mitoKCa的关闭有利于线粒体内膜中铊离子（Tl⁺）诱导的MPTP开放。
