Critical role of sodium in cytosolic [Ca2+] elevations in cultured hippocampal CA1 neurons during anoxic depolarization
Critical role of sodium in cytosolic [Ca2+] elevations in cultured hippocampal CA1 neurons during anoxic depolarization
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DOI：
10.1111/j.1471-4159.2006.04308.x
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发表时间：
2007-02-01
影响因子：
4.7
通讯作者：
Kiedrowski, Lech
中科院分区：
文献类型：
--
作者：
Kiedrowski, Lech
Although the extent of ischemic brain damage is directly proportional to the duration of anoxic depolarization (AD), the mechanism of cytosolic [Ca2+] ([Ca2+](c)) elevation during AD is poorly understood. To address the mechanism in this study, [Ca2+] c was monitored in cultured rat hippocampal CA1 neurons loaded with a Ca-sensitive dye, fura-2FF, and exposed to an AD-simulating medium containing (in mmol/L): K+ 65, Na+ 50, Ca2+ 0.13, glutamate 0.1, and pH reduced to 6.6. Application of this medium promptly elevated [Ca2+](c) to about 30 mu mol/L, but only if oxygen was removed, the respiratory chain was inhibited, or if the mitochondria were uncoupled. These high [Ca2+](c) elevations depended on external Ca2+ and could not be prevented by inhibiting NMDA or alpha-amino3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptors, or gadolinium-sensitive channels. However, they could be prevented by removing external Na+ or simultaneously inhibiting NMDA and AMPA/kainate receptors; 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl] isothiourea methanesulfonate (KB-R7943), an inhibitor of plasmalemmal Na+/Ca2+ exchanger, partly suppressed them. The data indicate that the [Ca2+](c) elevations to 30 mu mol/L during AD result from Na+ influx. Activation of either NMDA or AMPA/kainate channels provides adequate Na+ influx to induce these [Ca2+](c) elevations, which are mediated by KB-R7943-sensitive and KB-R7943-resistant mechanisms.
