Different oxidants and PKC isozymes mediate the opposite effect of inhibition of Q(i) and Q(o) site of mitochondrial complex III on calcium currents in rat cortical neurons.
Different oxidants and PKC isozymes mediate the opposite effect of inhibition of Q(i) and Q(o) site of mitochondrial complex III on calcium currents in rat cortical neurons.
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DOI：
10.1016/j.bbamcr.2010.05.001
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发表时间：
2010-09
期刊：
影响因子：
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通讯作者：
Pei-Ying Wu;B. Lai;Yi Dong;Ze-min Wang;Zicheng Li;P. Zheng
中科院分区：
文献类型：
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作者：
Pei-Ying Wu;B. Lai;Yi Dong;Ze-min Wang;Zicheng Li;P. Zheng
观察到缺氧缺血对线粒体呼吸链复合物III的抑制作用。然而，这种抑制的下游事件仍有待研究。本文采用全细胞膜片钳法对大鼠额叶神经元电压门控Ca2+电流（ICa）进行切片研究，利用Qisite抑制剂抗霉素A和qsite抑制剂myxothiazol抑制Qisite和Qosite复合物III，并研究这些位点的抑制作用及其机制。结果表明，抗霉素A抑制ICa，而粘噻唑使其升高。进一步的机制研究表明，抗霉素A抑制了ICavia的h2o2 -羟基自由基/cPKC（主要是PKCβI）通路，而粘噻唑则增加了ICavia的超氧阴离子/nPKC（主要是PKCδ）通路。
The inhibition of the complex III of the mitochondrial respiratory chain under hypoxia-ischemia has been observed. However, the downstream events of this inhibition remain to be studied. In this paper, we used the Qisite inhibitor antimycin A and the Qosite inhibitor myxothiazol to inhibit the Qisite and the Qosite of the complex III and studied the effect and mechanism of the inhibition of these sites on voltage-gated Ca2+currents (ICa) in rat prefrontal neurons with whole cell patch-clamp method in slices. The results showed that antimycin A inhibited ICa, but myxothiazol increased it. Further mechanism study showed that antimycin A inhibited ICavia the H2O2-hydroxyl radicals/cPKC (mainly PKCβI) pathway, whereas myxothiazol increased ICavia the superoxide anion/nPKC (mainly the PKCδ) pathway.