Nicorandil attenuates the mitochondrial Ca2+ overload with accompanying depolarization of the mitochondrial membrane in the heart
Nicorandil attenuates the mitochondrial Ca2+ overload with accompanying depolarization of the mitochondrial membrane in the heart
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DOI：
10.1007/s00210-003-0851-z
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发表时间：
2004-02-01
影响因子：
3.6
通讯作者：
Sato, T
中科院分区：
文献类型：
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作者：
Ishida, H;Higashijima, N;Sato, T
抗心绞痛药物尼可地尔在实验和临床研究中已被证明具有保护心肌免受缺血性损伤的作用。尽管尼可地尔似乎通过激活线粒体ATP敏感的K+ (mitoK(ATP))通道来保护心肌，但其保护心脏的机制仍然难以捉摸。因此，我们研究了尼可地尔是否使线粒体膜去极化并减弱线粒体Ca2+超载。采用Nipkow共聚焦系统，分别用rhod-2和JC-1加载细胞，测定大鼠心室肌细胞线粒体Ca2+浓度（[Ca2+](m)）和线粒体膜电位（DeltaPsi(m)）。计算由线粒体Ca2+超载引起的细胞过度收缩的数量。将细胞暴露于瓦阿因（1 mM）中可引起线粒体Ca2+过载，并将rhod-2荧光强度提高到基线的180+/-15% （p . 1）
The anti-anginal drug nicorandil has been demonstrated to protect the myocardium against ischemic injury in both experimental and clinical studies. Although nicorandil seems to protect the myocardium via activation of mitochondrial ATP-sensitive K+ (mitoK(ATP)) channels, the mechanisms underlying its cardioprotection have remained elusive. We therefore examined whether nicorandil depolarizes the mitochondrial membrane and attenuates the mitochondrial Ca2+ overload. With the use of a Nipkow confocal system, the mitochondrial Ca2+ concentration ([Ca2+](m)) and the mitochondrial membrane potential (DeltaPsi(m)) in rat ventricular myocytes were measured by loading cells with rhod-2 and JC-1 respectively. The number of cell hypercontractures resulting from mitochondrial Ca2+ overload was counted. Exposing cells to ouabain (1 mM) evoked mitochondrial Ca2+ overload and increased the intensity of rhod-2 fluorescence to 180+/-15% of baseline (p