The mitochondrial membrane potential and Ca2+ oscillations in smooth muscle
The mitochondrial membrane potential and Ca2+ oscillations in smooth muscle
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DOI：
10.1242/jcs.014522
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发表时间：
2008-01-01
影响因子：
4
通讯作者：
McCarron, John G.
中科院分区：
文献类型：
--
作者：
Chalmers, Susan;McCarron, John G.
线粒体对Ca~（2+）的摄取既可调节胞浆Ca~（2+）浓度（[Ca~（2+）]（c）），又可降低线粒体膜电位（Δ Psi（m）），从而限制ATP的产生。为了研究生理Ca2+信号传导如何影响能量产生，在平滑肌细胞中的Ca2+振荡期间检查Δ Psi（m）。在单个电压钳位平滑肌细胞中，抑制线粒体Ca2+积累可抑制肌醇（1，4，5）-三磷酸[Ins（1，4，（5）P-3]-激活质膜Ca~（2+）电流（I-Ca）后，引起[Ca~（2+）]释放，并延长[Ca~（2+）]恢复所需的时间（c）（15秒内）在Ins（1，4，5）P-3或ICa诱发[Ca~（2+）] c升高后。尽管有线粒体Ca2+积累的证据，但在这些条件引起的单一或重复[Ca2 +]（c）振荡期间，未观察到Δ Psi（m）的变化。偶尔，观察到自发的，重复的，持续的Ca2+振荡。在这些情况下，线粒体显示随机Δ Psi（m）去极化，这是独立的事件在相邻的线粒体和[Ca2 +]（c）振荡本身的时间。这种Δ Psi（m）去极化可以通过增加暴露于荧光激发光或Δ Psi（m）敏感染料四甲基罗丹明乙酯（TMRE）来模拟，并且被抗氧化剂（抗坏血酸、过氧化氢酶、Trolox和TEMPO）或线粒体渗透性转换孔（mPTP）抑制剂环孢菌素A（CsA）抑制。平滑肌细胞内的单个线粒体可能在重复的Ca 2+振荡或氧化应激期间去极化，但在由Ca 2+内流或储存释放引起的单一[Ca 2 +]（c）瞬变过程中不去极化。
Ca2+ uptake by mitochondria might both modulate the cytosolic Ca2+ concentration ([Ca2+](c)) and depolarize the mitochondrial membrane potential (Delta Psi(m)) to limit ATP production. To investigate how physiological Ca2+ signaling might affect energy production, Delta Psi(m) was examined during Ca2+ oscillations in smooth muscle cells. In single, voltage-clamped smooth muscle cells, inhibition of mitochondrial Ca2+ accumulation inhibited inositol (1,4,5)-trisphosphate [Ins(1,4,5) P-3]-evoked Ca2+ release and prolonged the time required for restoration of [Ca2+](c) following activation of plasmalemmal Ca2+ currents (I-Ca).Ca2+ could be released from mitochondria immediately ( within 15 seconds) after a [Ca2+] c rise evoked by Ins(1,4,5)P-3 or ICa. Despite this evidence of mitochondrial Ca2+ accumulation, no change in Delta Psi(m) was observed during single or repetitive [Ca2+](c) oscillations evoked by these conditions. Occasionally, spontaneous, repetitive, persistent Ca2+ oscillations were observed. In these cases, mitochondria displayed stochastic Delta Psi(m) depolarizations, which were independent both of events in neighboring mitochondria and of the timing of the [Ca2+](c) oscillations themselves. Such Delta Psi(m) depolarizations could be mimicked by increased exposure to either fluorescence excitation light or the Delta Psi(m)-sensitive dye tetramethylrhodamine ethyl ester (TMRE) and were inhibited by antioxidants (ascorbic acid, catalase, Trolox and TEMPO) or the mitochondrial permeability transition pore (mPTP)inhibitor cyclosporin A (CsA). Individual mitochondria within smooth muscle cells might depolarize during repetitive Ca2+ oscillations or during oxidative stress but not during the course of single [Ca2+](c) transients evoked by Ca2+ influx or store release.