Huang H M, Toral-Barza L, Sheu K F, Gibson G E
Department of Neurology and Neuroscience, Cornell University Medical College, Burke Medical Research Institute, White Plains, New York 10605.
Neurochem Res. 1994 Jan;19(1):89-95. doi: 10.1007/BF00966734.
Calcium homeostasis and mitochondrial oxidative metabolism interact closely in brain and both processes are impaired during hypoxia. Since the regulation of the pyruvate dehydrogenase complex (PDHC) may link these two processes, the relation of cytosolic free calcium ([Ca2+]i) to the activation state of PDHC (PDHa) was assessed in isolated nerve terminals (i.e. synaptosomes) under conditions that alter [Ca2+]i. K+ depolarization elevated [Ca2+]i and PDHa and both responses required external calcium. Treatment with KCN, an in vitro model of hypoxia decreased ATP and elevated [Ca2+]i and PDHa. Furthermore, in the presence of KCN, PDHa became more sensitive to K+ depolarization as indicated by larger changes in PDHa than in [Ca2+]i. The calcium ionophore Br-A23187 elevated [Ca2+]i, but did not affect PDHa. K+ depolarization elevated [Ca2+]i and PDHa even if [Ca2+]i was elevated by prior addition of ionophore or KCN. Previous in vivo studies by others show that PDHa is altered during and after ischemia. The current in vitro results suggest that hypoxia, only one component of ischemia, is sufficient to increase PDHa. These data also further support the notion that PDHa is regulated by [Ca2+]i as well as by other factors such as ATP. Our results are consistent with the concept that PDHa in nerve endings may be affected by [Ca2+]i and that these two processes are clearly linked.
钙稳态与线粒体氧化代谢在大脑中密切相互作用，且在缺氧过程中这两个过程均受损。由于丙酮酸脱氢酶复合体（PDHC）的调节可能将这两个过程联系起来，因此在改变胞质游离钙（[Ca2+]i）的条件下，在分离的神经末梢（即突触体）中评估了[Ca2+]i与PDHC激活状态（PDHa）之间的关系。钾离子去极化升高了[Ca2+]i和PDHa，且这两种反应均需要细胞外钙。用KCN处理（一种缺氧的体外模型）可降低ATP并升高[Ca2+]i和PDHa。此外，在存在KCN的情况下，PDHa对钾离子去极化变得更加敏感，这表现为PDHa的变化大于[Ca2+]i的变化。钙离子载体Br-A23187升高了[Ca2+]i，但不影响PDHa。即使通过预先添加离子载体或KCN使[Ca2+]i升高，钾离子去极化仍可升高[Ca2+]i和PDHa。其他人先前的体内研究表明，缺血期间及之后PDHa会发生改变。目前的体外研究结果表明，缺氧（缺血的一个组成部分）足以增加PDHa。这些数据还进一步支持了PDHa受[Ca2+]i以及其他因素（如ATP）调节的观点。我们的结果与神经末梢中的PDHa可能受[Ca2+]i影响且这两个过程明显相关的概念一致。
