Functional Role of Vanilloid Transient Receptor Potential 4-Canonical Transient Receptor Potential 1 Complex in Flow-Induced Ca2+ Influx
Functional Role of Vanilloid Transient Receptor Potential 4-Canonical Transient Receptor Potential 1 Complex in Flow-Induced Ca2+ Influx
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DOI：
10.1161/atvbaha.109.196584
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发表时间：
2010-04-01
影响因子：
8.7
通讯作者：
Yao, Xiaoqiang
中科院分区：
文献类型：
--
作者：
Ma, Xin;Qiu, Shuang;Yao, Xiaoqiang
本研究旨在研究TRPV 4与TRPC 1的相互作用以及这种相互作用在流动诱导的Ca 2+内流中的功能作用。血液动力学血流是调节血管张力的重要生理因素。在这个过程中的一个关键的早期事件是一个胞质Ca 2+（[Ca 2 +]（i））上升在内皮细胞中响应flow.Methods和Results-With使用的荧光共振能量转移，coimmunoprecipitation，和亚细胞共定位方法，它被发现，TRPC 1相互作用与TRPV 4物理形成一个复合物。在功能研究中，血流引起TRPV 4表达的人胚肾（HEK）293细胞瞬时[Ca 2 +]（i）增加。TRPC 1与TRPV 4的共表达显著延长了这种[Ca 2 +]（i）瞬变;它也使这种[Ca 2 +]（i）瞬变受到蛋白激酶G的负调节。此外，在TRPV 4-C1共表达的HEK细胞和人脐静脉内皮细胞中，抗TRPC 1阻断抗体T1 E3和显性阴性构建体TRPC 1 Delta 567-793显著抑制了这种流动诱导的[Ca 2 +]（i）增加。T1 E3也抑制了在离体大鼠小肠系膜动脉segments.Conclusion-This研究表明，TRPC 1与TRPV 4物理相互作用，形成一个复杂的，这个TRPV 4-C1复合物可能介导的流量诱导的血管内皮细胞内流Ca 2+内流。TRPC 1与TRPV 4的结合阻断了血流诱导的[Ca 2 +]（i）瞬变，并且它还使得该[Ca 2 +]（i）瞬变能够被蛋白激酶G负性调节。该TRPV 4-C1复合物在血流诱导的内皮Ca 2+内流中起关键作用。（Arterioscler Thromb Vasc Biol.2010; 30：851-858.）
Objective-The present study is aimed at investigating the interaction of TRPV4 with TRPC1 and the functional role of such an interaction in flow-induced Ca2+ influx. Hemodynamic blood flow is an important physiological factor that modulates vascular tone. One critical early event in this process is a cytosolic Ca2+ ([Ca2+](i)) rise in endothelial cells in response to flow.Methods and Results-With the use of fluorescence resonance energy transfer, coimmunoprecipitation, and subcellular colocalization methods, it was found that TRPC1 interacts physically with TRPV4 to form a complex. In functional studies, flow elicited a transient [Ca2+](i) increase in TRPV4-expressing human embryonic kidney (HEK) 293 cells. Coexpression of TRPC1 with TRPV4 markedly prolonged this [Ca2+](i) transient; it also enabled this [Ca2+](i) transient to be negatively modulated by protein kinase G. Furthermore, this flow-induced [Ca2+](i) increase was markedly inhibited by anti-TRPC1-blocking antibody T1E3 and a dominant-negative construct TRPC1 Delta 567-793 in TRPV4-C1-coexpressing HEK cells and human umbilical vein endothelial cells. T1E3 also inhibited flow-induced vascular dilation in isolated rat small mesenteric artery segments.Conclusion-This study shows that TRPC1 interacts physically with TRPV4 to form a complex, and this TRPV4-C1 complex may mediate flow-induced Ca2+ influx in vascular endothelial cells. The association of TRPC1 with TRPV4 prolongs the flow-induced [Ca2+](i) transient, and it also enables this [Ca2+](i) transient to be negatively modulated by protein kinase G. This TRPV4-C1 complex plays a key role in flow-induced endothelial Ca2+ influx. (Arterioscler Thromb Vasc Biol. 2010; 30: 851-858.)