Distinct characteristics of Ca(2+)-induced depolarization of isolated brain and liver mitochondria.
Distinct characteristics of Ca(2+)-induced depolarization of isolated brain and liver mitochondria.
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DOI：
10.1016/j.bbabio.2005.07.006
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发表时间：
2005-09
期刊：
影响因子：
--
通讯作者：
O. Vergun;I. Reynolds
中科院分区：
文献类型：
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作者：
O. Vergun;I. Reynolds
本文研究了钙离子对大鼠脑和肝线粒体的去极化作用。线粒体膜电位测定采用数字成像技术和罗丹明123。低浓度的Ca~(2+)(约30~100 nM)引起脑线粒体膜电位的振荡，随后线粒体完全去极化。相反，肝线粒体对Ca~(2+)的敏感性较低；需要20μM Ca~(2+)使肝线粒体去极化。Ca~(2+)不引起肝脏线粒体的振荡性去极化，每个线粒体的去极化都是突然的、不可逆转的。腺嘌呤核苷酸显著降低脑线粒体的振荡性去极化，并延迟肝线粒体去极化的开始。在两种类型的线粒体中，腺嘌呤核苷酸的稳定作用均被羧基苍术苷抑制腺嘌呤核苷酸转运体功能所完全消除，但对bongkrekic酸不敏感。线粒体通透性转换的抑制剂环孢素A和bongkrekic酸也延缓了钙离子的去极化。我们假设，脑线粒体的振荡性去极化与腺核苷酸转运体从特定转运体到非特异性孔的瞬间构象变化有关，而肝线粒体的非振荡去极化是由孔的不可逆开放引起的。
Ca2+-induced mitochondrial depolarization was studied in single isolated rat brain and liver mitochondria. Digital imaging techniques and rhodamine 123 were used for mitochondrial membrane potential measurements. Low Ca2+concentrations (about 30–100 nM) initiated oscillations of the membrane potential followed by complete depolarization in brain mitochondria. In contrast, liver mitochondria were less sensitive to Ca2+; 20 μM Ca2+was required to depolarize liver mitochondria. Ca2+did not initiate oscillatory depolarizations in liver mitochondria, where each individual mitochondrion depolarized abruptly and irreversibly. Adenine nucleotides dramatically reduced the oscillatory depolarization in brain mitochondria and delayed the onset of the depolarization in liver mitochondria. In both type of mitochondria, the stabilizing effect of adenine nucleotides completely abolished by an inhibition of adenine nucleotide translocator function with carboxyatractyloside, but was not sensitive to bongkrekic acid. Inhibitors of mitochondrial permeability transition cyclosporine A and bongkrekic acid also delayed Ca2+-depolarization. We hypothesize that the oscillatory depolarization in brain mitochondria is associated with the transient conformational change of the adenine nucleotide translocator from a specific transporter to a non-specific pore, whereas the non-oscillatory depolarization in liver mitochondria is caused by the irreversible opening of the pore.