Volume regulated anion channel currents of rat hippocampal neurons and their contribution to oxygen-and-glucose deprivation induced neuronal death.
Volume regulated anion channel currents of rat hippocampal neurons and their contribution to oxygen-and-glucose deprivation induced neuronal death.
复制标题
体积调节大鼠海马神经元的阴离子通道电流及其对氧和葡萄糖剥夺引起的神经元死亡的贡献。
DOI：
10.1371/journal.pone.0016803
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发表时间：
2011-02-11
期刊：
影响因子：
3.7
通讯作者：
Zhou M
中科院分区：
文献类型：
--
作者：
Zhang H;Cao HJ;Kimelberg HK;Zhou M
体积调节阴离子通道（VRAC）是广泛表达的氯离子通道，在细胞体积调节中起着至关重要的作用。在哺乳动物中枢神经系统中，神经元VRAC的生理表达及其在脑缺血中的作用在很大程度上是未知的。我们发现低渗介质诱导大鼠海马CA1锥体神经元向外整流氯离子电导。诱导氯离子电导对部分VRAC抑制剂IAA-94（300µM）和NPPB（100µM）敏感，但对他莫昔芬（10µM）不敏感。使用氧糖剥夺（OGD）模拟切片缺血情况，在OGD诱导的缺氧去极化（AD）后出现VRAC激活，在OGD再灌注后的一段时间内电流幅度逐渐增加。OGD溶液中谷氨酸AMPA（30µM NBQX）和NMDA（40µM AP-5）受体抑制剂显著抑制了OGD诱导的VRAC电流，这支持了AD的诱导需要通过这些受体过量加载Na+从而激活神经元VRAC的观点。在OGD后再灌注溶液中存在NPPB和DCPIB时，通过to - pro -3- i染色测量，OGD诱导的CA1锥体神经元死亡明显减少，尽管DCPIB似乎不是有效的神经元VRAC阻断剂。总之，我们发现大鼠海马锥体神经元表达功能性VRAC，缺血条件可以初始化神经元VRAC激活，从而可能导致缺血性神经元损伤。
Volume-regulated anion channels (VRAC) are widely expressed chloride channels that are critical for the cell volume regulation. In the mammalian central nervous system, the physiological expression of neuronal VRAC and its role in cerebral ischemia are issues largely unknown. We show that hypoosmotic medium induce an outwardly rectifying chloride conductance in CA1 pyramidal neurons in rat hippocampal slices. The induced chloride conductance was sensitive to some of the VRAC inhibitors, namely, IAA-94 (300 µM) and NPPB (100 µM), but not to tamoxifen (10 µM). Using oxygen-and-glucose deprivation (OGD) to simulate ischemic conditions in slices, VRAC activation appeared after OGD induced anoxic depolarization (AD) that showed a progressive increase in current amplitude over the period of post-OGD reperfusion. The OGD induced VRAC currents were significantly inhibited by inhibitors for glutamate AMPA (30 µM NBQX) and NMDA (40 µM AP-5) receptors in the OGD solution, supporting the view that induction of AD requires an excessive Na+-loading via these receptors that in turn to activate neuronal VRAC. In the presence of NPPB and DCPIB in the post-OGD reperfusion solution, the OGD induced CA1 pyramidal neuron death, as measured by TO-PRO-3-I staining, was significantly reduced, although DCPIB did not appear to be an effective neuronal VRAC blocker. Altogether, we show that rat hippocampal pyramidal neurons express functional VRAC, and ischemic conditions can initial neuronal VRAC activation that may contribute to ischemic neuronal damage.
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影响因子：
5.3
作者：
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