Fluoride Induces a Volume Reduction in CA1 Hippocampal Slices Via MAP Kinase Pathway Through Volume Regulated Anion Channels.
Fluoride Induces a Volume Reduction in CA1 Hippocampal Slices Via MAP Kinase Pathway Through Volume Regulated Anion Channels.
复制标题
DOI：
10.5607/en.2016.25.2.72
复制
发表时间：
2016-04
影响因子：
2.4
通讯作者：
Lee CJ
中科院分区：
文献类型：
--
作者：
Lee J;Han YE;Favorov O;Tommerdahl M;Whitsel B;Lee CJ
细胞体积的调节是神经活动期间细胞内稳态的重要方面。这种容量调节被认为是由特定转运蛋白、水通道蛋白和容量调节阴离子通道（VRAC）的激活介导的。在培养的星形胶质细胞中，据报道，肿胀诱导的丝裂原活化蛋白（MAP）激酶激活是打开VRAC所必需的，这被认为在调节性体积减小以及CNS对创伤和兴奋性毒性的反应中是重要的。也已经描述了氟化钠（NaF），一种公认的G-蛋白激活剂和蛋白磷酸酶抑制剂，导致内皮细胞中显著的MAP激酶激活。然而，NaF在脑容量调节中的作用尚不清楚。在这里，我们研究了氟化钠诱导的体积变化的机制，在大鼠和小鼠海马脑片使用固有光信号（IOS）记录，其中我们测量的相对变化，细胞内和细胞外的体积通过脑片的透光率的变化。我们发现，NaF（1~5 mM）应用诱导CA 1海马透光率降低（体积减少），MAP激酶抑制剂U 0126（10 µM）可完全逆转。我们还观察到NaF诱导的体积减少被阴离子通道阻断剂阻断，这表明NaF诱导的体积减少可以由VRAC介导。总之，我们的研究结果提出了一种新的分子机制，氟化钠诱导的体积减少通过MAP激酶信号通路激活VRAC。
Regulation of cell volume is an important aspect of cellular homeostasis during neural activity. This volume regulation is thought to be mediated by activation of specific transporters, aquaporin, and volume regulated anion channels (VRAC). In cultured astrocytes, it was reported that swelling-induced mitogen-activated protein (MAP) kinase activation is required to open VRAC, which are thought to be important in regulatory volume decrease and in the response of CNS to trauma and excitotoxicity. It has been also described that sodium fluoride (NaF), a recognized G-protein activator and protein phosphatase inhibitor, leads to a significant MAP kinase activation in endothelial cells. However, NaF's effect in volume regulation in the brain is not known yet. Here, we investigated the mechanism of NaF-induced volume change in rat and mouse hippocampal slices using intrinsic optical signal (IOS) recording, in which we measured relative changes in intracellular and extracellular volume as changes in light transmittance through brain slices. We found that NaF (1~5 mM) application induced a reduction in light transmittance (decreased volume) in CA1 hippocampus, which was completely reversed by MAP kinase inhibitor U0126 (10 µM). We also observed that NaF-induced volume reduction was blocked by anion channel blockers, suggesting that NaF-induced volume reduction could be mediated by VRAC. Overall, our results propose a novel molecular mechanism of NaF-induced volume reduction via MAP kinase signaling pathway by activation of VRAC.