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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >A possible pivotal role of mitochondrial free calcium in neurotoxicity mediated by N-methyl-d-aspartate receptors in cultured rat hippocampal neurons.
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A possible pivotal role of mitochondrial free calcium in neurotoxicity mediated by N-methyl-d-aspartate receptors in cultured rat hippocampal neurons.

机译：线粒体游离钙在培养的大鼠海马神经元中由N-甲基-d-天冬氨酸受体介导的神经毒性中的可能关键作用。

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摘要

We have previously shown that mitochondrial membrane potential disruption is involved in mechanisms underlying differential vulnerabilities to the excitotoxicity mediated by N-methyl-d-aspartate (NMDA) receptors between primary cultured neurons prepared from rat cortex and hippocampus. To further elucidate the role of mitochondria in the excitotoxicity after activation of NMDA receptors, neurons were loaded with the fluorescent dye calcein diffusible in the cytoplasm and organelles for determination of the activity of mitochondrial permeability transition pore (mPTP) responsible for the leakage of different mitochondrial molecules. The addition of CoCl(2) similarly quenched the intracellular fluorescence except mitochondria in both cultured neurons, while further addition of NMDA led to a leakage of the dye into the cytoplasm in hippocampal neurons only. An mPTP inhibitor prevented the NMDA-induced loss of viability in hippocampal neurons, while an activator of mPTP induced a similarly potent loss of viability in cortical and hippocampal neurons. Although NMDA was more effective in increasing rhodamine-2 fluorescence as a mitochondrial calcium indicator in hippocampal than cortical neurons, a mitochondrial calcium uniporter inhibitor significantly prevented the NMDA-induced loss of viability in hippocampal neurons. Expression of mRNA was significantly higher for the putative uniporter uncoupling protein-2 in hippocampal than cortical neurons. These results suggest that mitochondrial calcium uniporter would be at least in part responsible for the NMDA neurotoxicity through a mechanism relevant to promotion of mPTP orchestration in hippocampal neurons.
机译：先前我们已经表明，线粒体膜电位破坏参与了由大鼠皮层和海马制备的主要培养神经元之间的N-甲基-d-天冬氨酸（NMDA）受体介导的兴奋性毒性差异脆弱性的潜在机制。为了进一步阐明线粒体在激活NMDA受体后的兴奋性毒性中的作用，向神经元加载了可扩散到细胞质和细胞器中的荧光染料钙黄绿素，以确定负责不同线粒体渗漏的线粒体通透性转化孔（mPTP）的活性分子。 CoCl（2）的添加类似地淬灭了两个培养的神经元中除线粒体之外的细胞内荧光，而进一步添加NMDA导致染料仅渗入海马神经元的细胞质中。 mPTP抑制剂阻止了NMDA诱导的海马神经元活力的丧失，而mPTP的激活剂诱导了皮质和海马神经元活力的类似降低。尽管NMDA比皮质神经元在增加作为海马线粒体钙指示剂的罗丹明-2荧光方面更有效，但线粒体钙单向抑制剂明显阻止了NMDA诱导的海马神经元活力的丧失。海马中假定的单向解偶联蛋白2的mRNA表达明显高于皮质神经元。这些结果表明，线粒体钙单向转运蛋白将通过与促进海马神经元mPTP编排相关的机制至少部分负责NMDA神经毒性。

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