Rapid Ca2+-dependent increase in oxygen consumption by mitochondria in single mammalian central neurons
Rapid Ca2+-dependent increase in oxygen consumption by mitochondria in single mammalian central neurons
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DOI：
10.1016/j.ceca.2004.11.005
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发表时间：
2005-04-01
期刊：
影响因子：
4
通讯作者：
Kasai, H
中科院分区：
文献类型：
--
作者：
Hayakawa, Y;Nemoto, T;Kasai, H
在神经元活动开始后的几分之一秒内，耗氧量增加，这种现象在活体大脑的功能成像研究中被称为“初始下降”。然而，导致耗氧量快速增加的细胞机制仍不清楚。我们现在已经使用双光子激发成像来表征单个神经元中的快速活性依赖性线粒体反应。这种方法允许在培养的单个小鼠浦肯野神经元中对单个线粒体进行同步荧光成像。当胞浆游离Ca ~（2+）浓度（[Ca ~（2+）]（i））超过15 μ M时，线粒体去极化立即被诱导，并与线粒体NAD（P）H的氧化有关，表明Ca ~（2+）诱导的线粒体去极化由Ca ~（2+）单向转运体介导，直接促进NAD（P）H的氧化。通过使用微型氧电极，我们检测到单个浦肯野神经元细胞去极化开始后0.2 s内的氧消耗爆发，这种氧消耗的快速增加依赖于[Ca 2 +]（i）的增加。因此，我们已经证明了一个快速的Ca 2+依赖性消耗的氧介导的线粒体去极化在哺乳动物中枢神经元。这一过程可能作为一种快速前馈机制在细胞内ATP浓度的稳态控制。(C)2005 Elsevier Ltd.保留所有权利。
Oxygen consumption increases within a fraction of a second after the onset of neuronal activity, a phenomenon referred to as the "initial dip" in functional imaging studies of the living brain. The cellular mechanism that underlies this rapid increase in oxygen consumption has remained unclear, however. We have now used two-photon excitation imaging to characterize rapid activity-dependent mitochondrial responses in single neurons. This approach allowed simultaneous multicolor imaging of individual mitochondria in single mouse Purkinje neurons in culture. Mitochondrial depolarization was induced immediately when the cytosolic free Ca2+ concentration ([Ca2+](i)) exceeded 15 mu M and was associated with oxidation of mitochondrial NAD(P)H, suggesting that Ca2+-induced mitochondrial depolarization mediated by the Ca2+ uniporter directly facilitated oxidation of NAD(P)H. With the use of a miniature oxygen electrode, we detected a burst of oxygen consumption within 0.2 s after the onset of cell depolarization in single Purkinje neurons, and this rapid increase in oxygen consumption was dependent on the increase in [Ca2+](i). We have thus demonstrated a rapid Ca2+-dependent consumption of oxygen that is mediated by mitochondrial depolarization in mammalian central neurons. This process might function as a rapid feed-forward mechanism in homeostatic control of the cytosolic ATP concentration. (C) 2005 Elsevier Ltd. All rights reserved.