Mitochondrial Ca2+-activated K+ channels more efficiently reduce mitochondrial Ca2+ overload in rat ventricular myocytes
Mitochondrial Ca2+-activated K+ channels more efficiently reduce mitochondrial Ca2+ overload in rat ventricular myocytes
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DOI：
10.1152/ajpheart.00789.2006
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发表时间：
2007-07-01
影响因子：
4.8
通讯作者：
Han, Jin
中科院分区：
文献类型：
--
作者：
Kang, Sung Hyun;Park, Won Sun;Han, Jin
我们研究了线粒体atp敏感K+ (KATP)通道、线粒体大电导Ca2+激活K+ (BKCa)通道和线粒体通透性过渡孔（MPTP）在瓦阿因诱导的天然大鼠心室肌细胞线粒体Ca2+增加中的作用。为了超载线粒体Ca2+，我们在使用线粒体KATP或BKCa通道和/或MPTP打开剂之前，用瓦巴因预处理细胞。瓦巴因（1 mM）可提高rho2敏感荧光强度（为对照的160 +/- 5.0%），二氮氧化物和NS-1619对rho2敏感荧光强度呈剂量依赖性显著降低至对照水平（二氮氧化物和NS-1619的半抑制浓度分别为78.3和7.78 μ M）。这种作用被5-羟基乙酸酯选择性抑制线粒体KATP通道、帕罗西林选择性抑制线粒体BKCa通道和环孢素a选择性抑制MPTP逆转。尽管在长时间暴露于瓦巴因时，二氮氧化物不能有效地降低线粒体Ca2+，但NS-1619降低了线粒体Ca2+。这些结果表明，尽管线粒体BKCa和KATP通道有助于减少瓦阿因诱导的线粒体Ca2+过载，但在我们的实验模型中，激活线粒体BKCa通道更有效地减少瓦阿因诱导的线粒体Ca2+过载。
We investigated the role of the mitochondrial ATP-sensitive K+ (KATP) channel, the mitochondrial big-conductance Ca2+-activated K+ (BKCa) channel, and the mitochondrial permeability transition pore ( MPTP) in the ouabain-induced increase of mitochondrial Ca2+ in native rat ventricular myocytes by loading cells with rhod 2-AM. To overload mitochondrial Ca2+, we pretreated cells with ouabain before applying mitochondrial KATP or BKCa channel and/or MPTP opener. Ouabain (1 mM) increased the rhod 2-sensitive fluorescence intensity (160 +/- 5.0% of control), which was dramatically decreased to the control level on application of diazoxide and NS-1619 in a dose-dependent manner (half-inhibition concentrations of 78.3 and 7.78 mu M for diazoxide and NS-1619, respectively). This effect was reversed by selective inhibition of the mitochondrial KATP channel by 5-hydroxydecanoate, the mitochondrial BKCa channel by paxilline, and the MPTP by cyclosporin A. Although diazoxide did not efficiently reduce mitochondrial Ca2+ during prolonged exposure to ouabain, NS-1619 reduced mitochondrial Ca2+. These results suggest that although mitochondrial BKCa and KATP channels contribute to reduction of ouabain-induced mitochondrial Ca2+ overload, activation of the mitochondrial BKCa channel more efficiently reduces ouabain-induced mitochondrial Ca2+ overload in our experimental model.