Transient mitochondrial depolarizations reflect focal sarcoplasmic reticular calcium release in single rat cardiomyocytes.
Transient mitochondrial depolarizations reflect focal sarcoplasmic reticular calcium release in single rat cardiomyocytes.
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DOI：
10.1083/jcb.142.4.975
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发表时间：
1998-08-24
期刊：
影响因子：
--
通讯作者：
Crompton M
中科院分区：
文献类型：
--
作者：
Duchen MR;Leyssens A;Crompton M
单个大鼠心肌细胞线粒体电位的数字成像揭示了细胞内线粒体的短暂去极化，我们将这种现象称为“闪烁”。这些事件通常高度局限于单个线粒体，但它们也可能在细胞内更广泛地分布。收缩波，无论是自发的还是对50mm K+去极化的反应，都与线粒体去极化的传播波有关，这表明传播钙波与线粒体钙摄取和随后的去极化有关。在这里，我们证明线粒体闪烁与肌浆网状（SR）钙储存的钙局部释放和随后局部线粒体对钙的摄取直接相关。因此，通过(a)在EGTA或thapsigargin （500 nM）中长期孵卵后SR钙储存的耗尽，这些事件显著减少；(b)利用BAPTA-AM负载缓冲细胞内钙；(c) ryanodine （30 μM）阻断SR钙释放；(d)微注射二氨基戊烷五胺钴（DAPPAC）阻断线粒体钙摄取，这是一种新的线粒体钙单转运抑制剂。这些观察结果表明，局部SR钙释放导致钙微域足以促进局部线粒体钙摄取，这表明SR释放位点与附近线粒体之间的钙信号密切耦合。
Digital imaging of mitochondrial potential in single rat cardiomyocytes revealed transient depolarizations of mitochondria discretely localized within the cell, a phenomenon that we shall call “flicker.” These events were usually highly localized and could be restricted to single mitochondria, but they could also be more widely distributed within the cell. Contractile waves, either spontaneous or in response to depolarization with 50 mM K+, were associated with propagating waves of mitochondrial depolarization, suggesting that propagating calcium waves are associated with mitochondrial calcium uptake and consequent depolarization. Here we demonstrate that the mitochondrial flicker was directly related to the focal release of calcium from sarcoplasmic reticular (SR) calcium stores and consequent uptake of calcium by local mitochondria. Thus, the events were dramatically reduced by (a) depletion of SR calcium stores after long-term incubation in EGTA or thapsigargin (500 nM); (b) buffering intracellular calcium using BAPTA-AM loading; (c) blockade of SR calcium release with ryanodine (30 μM); and (d) blockade of mitochondrial calcium uptake by microinjection of diaminopentane pentammine cobalt (DAPPAC), a novel inhibitor of the mitochondrial calcium uniporter. These observations demonstrate that focal SR calcium release results in calcium microdomains sufficient to promote local mitochondrial calcium uptake, suggesting a tight coupling of calcium signaling between SR release sites and nearby mitochondria.
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