Peterson C, Nicholls D G, Gibson G E
J Neurochem. 1985 Dec;45(6):1779-90. doi: 10.1111/j.1471-4159.1985.tb10534.x.
Previous results demonstrate that hypoxia (low oxygen) diminishes calcium uptake by synaptosomes. The present studies examined the effects of low oxygen on calcium homeostasis in the digitonin-resistant (mitochondrial) and the digitonin-labile (nonmitochondrial) compartments of intact synaptosomes and their relation to altered membrane potentials. A 10-min hypoxic incubation in low-potassium media reduced total (-38.3%), mitochondrial (-43.3%), and nonmitochondrial (-27.8%) calcium uptake. In high-potassium media, low oxygen reduced mitochondrial (-41.2%) and total (-34.4%) uptake whereas nonmitochondrial (+ 6%) calcium uptake was essentially unaffected. A temporal analysis of nonmitochondrial calcium uptake revealed an initial depression (0-5 min) followed by a stimulation (5-10 min). Hypoxic-induced alterations in the subsynaptosomal distribution of calcium resembled those produced by uncouplers [FCCP (carbonylcyanide-p-trifluoromethoxyphenylhydrazone) or rotenone plus oligomycin]. 3,4-Diaminopyridine partially ameliorated the hypoxic- and FCCP-induced decreases in synaptosomal calcium uptake. Low oxygen reduced the total synaptosomal membrane potential (i.e., plasma plus mitochondrial membrane potential) as measured by an increased efflux of tetraphenylphosphonium ion. This hypoxic-induced efflux of tetraphenylphosphonium was slowed by pretreatment with 3,4-diaminopyridine. Thus, both drug and membrane potential studies suggest that hypoxic-induced alterations in the subcellular distribution of calcium may be due to an uncoupling mechanism and a collapse of the synaptosomal mitochondrial membrane potential.
先前的研究结果表明，缺氧（低氧）会减少突触体对钙的摄取。本研究检测了低氧对完整突触体中对皂角苷有抗性的（线粒体）和对皂角苷敏感的（非线粒体）区室钙稳态的影响，以及它们与膜电位改变的关系。在低钾培养基中进行10分钟的缺氧孵育可降低总钙摄取量（-38.3%）、线粒体钙摄取量（-43.3%）和非线粒体钙摄取量（-27.8%）。在高钾培养基中，低氧降低了线粒体钙摄取量（-41.2%）和总钙摄取量（-34.4%），而非线粒体钙摄取量（+6%）基本未受影响。对非线粒体钙摄取的时间分析显示，最初有一个下降阶段（0 - 5分钟），随后是一个上升阶段（5 - 10分钟）。缺氧诱导的突触体下钙分布变化类似于解偶联剂[羰基氰化物-对-三氟甲氧基苯腙（FCCP）或鱼藤酮加寡霉素]所产生的变化。3,4 - 二氨基吡啶部分改善了缺氧和FCCP诱导的突触体钙摄取减少。低氧降低了通过四苯基鏻离子外流增加所测量的总突触体膜电位（即质膜加线粒体膜电位）。用3,4 - 二氨基吡啶预处理可减缓这种缺氧诱导的四苯基鏻外流。因此，药物和膜电位研究均表明，缺氧诱导的亚细胞钙分布变化可能是由于解偶联机制和突触体线粒体膜电位的崩溃。
