Cardioprotective effects of estradiol include the activation of large-conductance Ca2+-activated K+ channels in cardiac mitochondria
Cardioprotective effects of estradiol include the activation of large-conductance Ca2+-activated K+ channels in cardiac mitochondria
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DOI：
10.1152/ajpheart.00016.2005
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发表时间：
2005-10-01
影响因子：
4.8
通讯作者：
Imaizumi, Y
中科院分区：
文献类型：
--
作者：
Ohya, S;Kuwata, Y;Imaizumi, Y
在心肌细胞线粒体（mitoK（Ca））中功能性表达的大电导Ca 2+激活的K+通道的分子组分尚未确定。我们的实验结果表明，对应于大电导钙激活钾通道β 1亚基（BK-β 1）的转录本在哺乳动物心脏中大量表达。酵母双杂交试验表明BK-β 1蛋白可以与线粒体蛋白细胞色素c氧化酶亚基I（Cco 1）相互作用。免疫细胞化学实验的结果也表明，BK-β 1与Cco 1相互作用，并共定位于大鼠心肌线粒体。此外，17 β-雌二醇，它增强BK通道α-亚基的活性，只有在β 1-亚基的存在下，显着增加大鼠心室肌细胞黄素蛋白氧化，并降低模拟缺血下的细胞死亡率。线粒体内膜的单通道记录表明，mitoK（Ca）的活性，具有类似于270 pS的电导，被17 β-雌二醇增强，并被paxilline阻断。总而言之，本研究揭示了17 β-雌二醇心脏保护作用的新机制，其中包括通过与BK-β 1的相互作用激活mitoK（Ca）。BK-β 1可能是一个重要的分子组成部分，与Cco 1和mitoK（Ca）孔形成α亚基功能耦合。
The molecular components of the large-conductance Ca2+-activated K+ channels that are functionally expressed in mitochondria (mitoK(Ca)) in cardiac myocytes have not been identified. Our experimental results show that the transcript corresponding to the large-conductance Ca2+-activated K+ channel beta 1-subunit (BK-beta 1) is substantially expressed in mammalian heart. A yeast two-hybrid assay showed the BK-beta 1 protein can interact with a mitochondrial protein, cytochrome c oxidase subunit I (Cco1). Results from immunocytochemical experiments also demonstrated that BK-beta 1 interacted with Cco1 and colocalized in rat cardiac mitochondria. Furthermore, 17 beta-estradiol, which enhances the activity of the BK channel alpha-subunit only in the presence of the beta 1-subunit, significantly increased flavoprotein oxidation in rat ventricle myocytes and decreased the rate of cell death under simulated ischemia. Single-channel recordings from mitochondrial inner membrane indicated that the activity of mitoK(Ca), which had a conductance of similar to 270 pS, was enhanced by 17 beta-estradiol and blocked by paxilline. In combination, the present study revealed a new mechanism for the cardioprotective effects of 17 beta-estradiol, which include the activation of mitoK(Ca) via the interaction with BK-beta 1. BK-beta 1 may be an important molecular component that functionally couples with both Cco1 and mitoK(Ca) pore-forming alpha-subunit.