Heteromeric TRPV4-C1 channels contribute to store-operated Ca(2+) entry in vascular endothelial cells.
Heteromeric TRPV4-C1 channels contribute to store-operated Ca(2+) entry in vascular endothelial cells.
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DOI：
10.1016/j.ceca.2011.08.006
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发表时间：
2011-12
期刊：
影响因子：
4
通讯作者：
Yao X
中科院分区：
文献类型：
--
作者：
Ma X;Cheng KT;Wong CO;O'Neil RG;Birnbaumer L;Ambudkar IS;Yao X
Trp通道是否参与调节钙离子内流(SOCE)和钙离子内流(SOCE)尚有争议。我们最近的研究表明，TRPC1与TRPV4在血管内皮细胞中形成异构体通道，而钙库的耗竭促进了异构体TRPV4-C1通道的囊泡转运，导致更多的通道插入血管内皮细胞的质膜。在本研究中，我们确定了增强的TRPV4-C1插入质膜是否有助于SOCE和ISOC。我们发现，与野生型小鼠相比，来自TRPV4−/−或TRPC1−/−基因敲除小鼠的主动脉内皮细胞由thapsigargin诱导的SOCE要低得多。在人脐静脉内皮细胞(HUVECs)中，通过下调TRPC1和/或TRPV4的表达，thapsigargin诱导的SOCE明显减少。囊泡转位的阻断剂Brefeldin A可抑制SOCE。这些结果表明，异构体TRPV4-C1通道的囊泡转运增强有助于血管内皮细胞的SOCE。血管张力研究表明，这种增强的TRPV4-C1通道的运输可能在thapsigargin诱导的大鼠肠系膜小动脉血管松弛中发挥作用。
There is controversy as to whether TRP channels participate in mediating store-operated current (ISOC) and store-operated Ca2+ entry (SOCE). Our recent study has demonstrated that TRPC1 forms heteromeric channels with TRPV4 in vascular endothelial cells and that Ca2+ store depletion enhances the vesicle trafficking of heteromeric TRPV4-C1 channels, causing insertion of more channels into the plasma membrane in vascular endothelial cells. In the present study, we determined whether the enhanced TRPV4-C1 insertion to the plasma membrane could contribute to SOCE and ISOC. We found that thapsigargin-induced SOCE was much lower in aortic endothelial cells derived from trpv4−/− or trpc1−/− knockout mice when compared to that of wild-type mice. In human umbilical vein endothelial cells (HUVECs), thapsigargin-induced SOCE was markedly reduced by knocking down the expression of TRPC1 and/or TRPV4 with respective siRNAs. Brefeldin A, a blocker of vesicular translocation, inhibited the SOCE. These results suggest that an enhanced vesicular trafficking of heteromeric TRPV4-C1 channels contributes to SOCE in vascular endothelial cells. Vascular tension studies suggest that such an enhanced trafficking of TRPV4-C1 channels may play a role in thapsigargin-induced vascular relaxation in rat small mesenteric arteries.
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影响因子：
3.5
作者：
Lee KP;Yuan JP;Hong JH;So I;Worley PF;Muallem S
通讯作者：
Muallem S
DOI：
10.1161/atvbaha.109.196584
发表时间：
2010-04-01
影响因子：
8.7
作者：
Ma, Xin;Qiu, Shuang;Yao, Xiaoqiang
通讯作者：
Yao, Xiaoqiang
影响因子：
4
作者：
Cayouette, Sylvie;Boulay, Guylain
通讯作者：
Boulay, Guylain
影响因子：
4.5
作者：
Dietrich, Alexander;Kalwa, Hermann;Gudermann, Thomas
通讯作者：
Gudermann, Thomas
DOI：
10.1161/atvbaha.110.212084
发表时间：
2010-11
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Ma X;Cao J;Luo J;Nilius B;Huang Y;Ambudkar IS;Yao X
通讯作者：
Yao X