Neurosteroid dehydroepiandrosterone sulphate inhibits persistent sodium currents in rat medial prefrontal cortex via activation of sigma-1 receptors
Neurosteroid dehydroepiandrosterone sulphate inhibits persistent sodium currents in rat medial prefrontal cortex via activation of sigma-1 receptors
复制标题
神经类固醇硫酸脱氢表雄酮通过激活 sigma-1 受体抑制大鼠内侧前额叶皮层的持续钠电流
DOI：
10.1016/j.expneurol.2007.10.004
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发表时间：
2008-03-01
影响因子：
5.3
通讯作者：
Zheng, Ping
中科院分区：
文献类型：
--
作者：
Cheng, Zheng-Xiang;Lan, Dan-Mei;Zheng, Ping
硫酸脱氢表雄酮是最重要的神经甾体之一。本文采用膜片钳全细胞记录技术结合药理学方法研究了硫酸脱氢表雄酮对大鼠内侧前额叶脑片持续性钠电流的影响及其机制和功能后果。结果表明，硫酸脱氢表雄酮对持续性钠电流的幅度有抑制作用，在0.1 μ M时抑制作用显著，在1 μ M时达到最大，并随上述浓度的增加而减弱。硫酸脱氢表雄酮对持续性钠电流的作用可被Gi蛋白抑制剂和蛋白激酶C抑制剂所抵消，但不被蛋白激酶A抑制剂所抵消。硫酸脱氢表雄酮对持续性钠电流的作用也被sigma-1受体阻断剂抵消，sigma-1受体激动剂可以模拟硫酸脱氢表雄酮的作用。硫酸脱氢表雄酮对神经元兴奋性无显著影响，但可显著抑制化学抑制法诱导的持续性钠电流增加。这些结果表明，硫酸脱氢表雄酮通过激活sigma-1受体-Gi蛋白-蛋白激酶C偶联信号通路抑制持续性钠电流，DHEAS这种作用的主要功能后果可能是保护缺血神经元。(c)2007年爱思唯尔公司All rights reserved.
Dehydroepiandrosterone sulphate is one of the most important neurosteroids. In the present paper, we studied the effect of dehydroepiandrosterone sulphate on persistent sodium currents and its mechanism and functional consequence with whole-cell patch clamp recording method combined with a pharmacological approach in the rat medial prefrontal cortex slices. The results showed that dehydroepiandrosterone sulphate inhibited the amplitude of persistent sodium currents and the inhibitory effect was significant at 0.1 mu M, reached maximum at 1 mu M and decreased with the increase in the concentrations of above I IN. The effect of dehydroepiandrosterone sulphate on persistent sodium currents was canceled by the Gi protein inhibitor and the protein kinase C inhibitor, but not by the protein kinase A inhibitor. The effect of dehydroepiandrosterone sulphate on persistent sodium currents was also canceled by the sigma-1 receptor blockers and the sigma-1 receptor agonist could mimic the effect of dehydroepiandrosterone sulphate. Dehydroepiandrosterone sulphate had no significant influence on neuronal excitability but could significantly inhibit chemical inhibition of mitochondria-evoked increase in persistent sodium currents. These results suggest that dehydroepiandrosterone sulphate inhibits persistent sodium currents via the activation of sigma-1 receptors-Gi protein-protein kinase C-coupled signaling pathway, and the main functional consequence of this effect of DHEAS is presumably to protect neurons under ischemia. (c) 2007 Elsevier Inc. All rights reserved.