Modulation of intracellular calcium waves and triggered activities by mitochondrial ca flux in mouse cardiomyocytes.
Modulation of intracellular calcium waves and triggered activities by mitochondrial ca flux in mouse cardiomyocytes.
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小鼠心肌细胞中线粒体 ca 通量对细胞内钙波的调节和触发活动。
DOI：
10.1371/journal.pone.0080574
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Xie LH
中科院分区：
文献类型：
--
作者：
Zhao Z;Gordan R;Wen H;Fefelova N;Zang WJ;Xie LH
最近的研究表明线粒体可能在心肌细胞的 Ca2+ 稳态中发挥重要作用。然而，目前尚不清楚线粒体 Ca2+ 通量是否可以调节 Ca2+ 波 (CaWs) 的产生并触发心肌细胞的活动。在本研究中，对加载 Fluo-4-AM 的小鼠心室肌细胞中的细胞内/胞质 Ca2+ (Cai 2+) 进行成像。在高 (4 mM) 外部 Ca2+ (Cao 2+) 存在下诱导自发肌浆网 (SR) Ca2+ 释放和 CaWs。即使在没有 Cao 2+ 的情况下 SR Ca2+ 耗尽后，质子载体羰基氰化物对（三氟甲氧基）苯腙 (FCCP) 仍可逆地升高基础 Cai 2+ 水平，表明 Ca2+ 从线粒体中释放。 0.01 - 0.1 µM 的 FCCP 部分去极化线粒体膜电位 (Δψ m)，并以剂量依赖性方式增加 CaW 的频率和幅度。细胞膜电位的同时记录显示延迟后除极幅度和频率的增加，以及触发动作电位的诱导。 FCCP 对 CaWs 的作用可以通过抗霉素 A（一种破坏 Δψ m 的电子传递链抑制剂）或 Ru360（一种线粒体 Ca2+ 单向转运蛋白抑制剂）来模拟，但不能通过寡霉素（一种 ATP 合酶抑制剂）或碘乙酸（一种糖酵解抑制剂）来模拟，排除细胞内 ATP 水平的影响。 FCCP 对 CaW 的影响被线粒体通透性转换孔阻断剂环孢菌素 A 或线粒体 Ca2+ 单向转运蛋白激活剂山奈酚抵消。我们的研究结果表明，线粒体 Ca2+ 释放和摄取精确控制 SR 兰尼碱受体附近微域中的局部 Ca2+ 水平，并在细胞内 CaW 和心律失常的调节中发挥重要作用。
Recent studies have suggested that mitochondria may play important roles in the Ca2+ homeostasis of cardiac myocytes. However, it is still unclear if mitochondrial Ca2+ flux can regulate the generation of Ca2+ waves (CaWs) and triggered activities in cardiac myocytes. In the present study, intracellular/cytosolic Ca2+ (Cai 2+) was imaged in Fluo-4-AM loaded mouse ventricular myocytes. Spontaneous sarcoplasmic reticulum (SR) Ca2+ release and CaWs were induced in the presence of high (4 mM) external Ca2+ (Cao 2+). The protonophore carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) reversibly raised basal Cai 2+ levels even after depletion of SR Ca2+ in the absence of Cao 2+ , suggesting Ca2+ release from mitochondria. FCCP at 0.01 - 0.1 µM partially depolarized the mitochondrial membrane potential (Δψ m) and increased the frequency and amplitude of CaWs in a dose-dependent manner. Simultaneous recording of cell membrane potentials showed the augmentation of delayed afterdepolarization amplitudes and frequencies, and induction of triggered action potentials. The effect of FCCP on CaWs was mimicked by antimycin A (an electron transport chain inhibitor disrupting Δψ m) or Ru360 (a mitochondrial Ca2+ uniporter inhibitor), but not by oligomycin (an ATP synthase inhibitor) or iodoacetic acid (a glycolytic inhibitor), excluding the contribution of intracellular ATP levels. The effects of FCCP on CaWs were counteracted by the mitochondrial permeability transition pore blocker cyclosporine A, or the mitochondrial Ca2+ uniporter activator kaempferol. Our results suggest that mitochondrial Ca2+ release and uptake exquisitely control the local Ca2+ level in the micro-domain near SR ryanodine receptors and play an important role in regulation of intracellular CaWs and arrhythmogenesis.
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影响因子：
4.3
作者：
Csordas, Gyoergy;Hajnoczky, Gyoergy
通讯作者：
Hajnoczky, Gyoergy
影响因子：
10.8
作者：
Hausenloy DJ;Lim SY;Ong SG;Davidson SM;Yellon DM
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4
作者：
De Giusti VC;Caldiz CI;Ennis IL;Pérez NG;Cingolani HE;Aiello EA
通讯作者：
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影响因子：
9.5
作者：
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通讯作者：
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影响因子：
25
作者：
Fluegge, Daniela;Moeller, Lisa M.;Spehr, Marc
通讯作者：
Spehr, Marc