[Pathophysiological roles of transient receptor potential channels in glial cells].
[Pathophysiological roles of transient receptor potential channels in glial cells].
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DOI：
10.1248/yakushi.130.281
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发表时间：
2010-03
期刊：
影响因子：
--
通讯作者：
H. Shirakawa;T. Nakagawa;S. Kaneko
中科院分区：
文献类型：
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作者：
H. Shirakawa;T. Nakagawa;S. Kaneko
神经胶质细胞在中枢神经系统中含量丰富，在神经元活动、血管功能和胶质递质释放的调节中发挥着不同的作用，而病理性激活的神经胶质细胞与Ca（2+）信号通路共同干扰脑功能，但对独特的Ca（2+）内流现象还没有足够的解释。瞬时受体电位（TRP）超家族包括一组非选择性阳离子通道，其响应于其环境中的不同刺激而打开。尽管TRP通道广泛分布于哺乳动物脑中，但其作用仍有待阐明。本文综述了TRP通道在病理生理过程中的作用，特别是神经胶质细胞中的TRPC 3和TRPV 4通道。使用大鼠皮质星形胶质细胞，我们发现TRPC 3通过TRPC 3本身的Ca（2+）信号被凝血酶上调。凝血酶还上调了S100 B（反应性星形胶质细胞的标志物），并增加了细胞增殖，这两者都被Ca（2+）信号传导阻断剂和使用siRNA特异性敲低TRPC 3所抑制，表明TRPC 3部分通过前馈上调其自身表达而导致星形胶质细胞的病理活化。此外，我们发现TRPV 4的激动剂4 α-PDD的刺激抑制LPS诱导的小胶质细胞活化，而TRPV 4 mRNA在LPS处理的培养大鼠小胶质细胞中下调。这些结果表明，TRP通道在星形胶质细胞和小胶质细胞的激活过程中发挥关键作用。
Glial cells are abundant in the CNS and play diverse roles in the regulation of neuronal activity, vascular function, and gliotransmitter release, whereas pathologically activated glial cells have been reported to disturb brain function in conjunction with Ca(2+) signaling, however there is no enough explanation for a unique Ca(2+) entry. Transient receptor potential (TRP) superfamily comprises a group of non-selective cation channels that open in response to divergent stimuli in their environment. Although TRP channels are widely distributed in the mammalian brain, their roles remain to be elucidated. Here we provide an overview of the roles of TRP channels in pathophysiological processes, especially focusing on TRPC3 and TRPV4 channels in glial cells. Using rat cortical astrocytes, we found that TRPC3 was upregulated by thrombin via Ca(2+) signaling through TRPC3 itself. Thrombin also upregulated S100B, a marker of reactive astrocytes, and increased cell proliferation, both of which were inhibited by Ca(2+) signaling blockers and specific knockdown of TRPC3 using siRNA, suggesting that TRPC3 contributes to the pathological activation of astrocytes in part through a feed-forward upregulation of its own expression. Moreover, we found that TRPV4 stimulation by its agonist 4alpha-PDD suppressed LPS-induced microglial activation while TRPV4 mRNA was downregulated in LPS-treated cultured rat microglia. These results suggest that TRP channels play pivotal roles in the process of astrocytic and microglial activation.