Functional Role of TRPV4-KCa2.3 Signaling in Vascular Endothelial Cells in Normal and Streptozotocin-Induced Diabetic Rats
Functional Role of TRPV4-KCa2.3 Signaling in Vascular Endothelial Cells in Normal and Streptozotocin-Induced Diabetic Rats
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TRPV4-KCa2.3 信号在正常和链脲佐菌素诱导的糖尿病大鼠血管内皮细胞中的功能作用
DOI：
10.1161/hypertensionaha.113.01500
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发表时间：
2013-07-01
期刊：
影响因子：
8.3
通讯作者：
Yao, Xiaoqiang
中科院分区：
文献类型：
--
作者：
Ma, Xin;Du, Juan;Yao, Xiaoqiang
已知小电导和中电导Ca2+激活的K+通道参与内皮依赖性超极化。Ca2+进入内皮细胞刺激这些通道，导致内皮细胞和下层平滑肌细胞的膜超极化。在本研究中，我们利用共免疫沉淀和双重免疫标记方法，在大鼠肠系膜动脉内皮细胞中证实了瞬时受体电位vanilloid 4 （TRPV4）与K(Ca)2.3的物理相互作用。乙酰胆碱和4-PDD主要通过TRPV4-K(Ca)2.3通路诱导平滑肌超极化和血管舒张。K(Ca)3.1也参与了这一过程，但程度远低于K(Ca)2.3。刺激TRPV4-K(Ca)2.3信号通路也增加了麻醉大鼠肠系膜床的局部血流量，降低了全身血压。在链脲佐菌素诱导的糖尿病大鼠中，TRPV4和K(Ca)2.3的表达水平降低，这可能是导致这些动物内皮依赖性超极化功能障碍的潜在原因。这些结果表明TRPV4-K(Ca)2.3信号通路在血管内皮细胞中具有重要的生理和病理作用。
The small conductance and intermediate conductance Ca2+-activated K+ channels are known to be involved in the endothelium-dependent hyperpolarization. Ca2+ entry into endothelial cells stimulates these channels, causing membrane hyperpolarization in endothelial cells and underlying smooth muscle cells. In the present study, with the use of coimmunoprecipitation and double immunolabeling methods, we demonstrated a physical interaction of transient receptor potential vanilloid 4 (TRPV4) with K(Ca)2.3 in rat mesenteric artery endothelial cells. Acetylcholine and 4-PDD mainly acted through TRPV4-K(Ca)2.3 pathway to induce smooth muscle hyperpolarization and vascular relaxation. K(Ca)3.1 was also involved in the process but at a much lesser degree than that of K(Ca)2.3. Stimulating TRPV4-K(Ca)2.3 signaling pathway also increased local blood flow in mesenteric beds and reduced systemic blood pressure in anesthetized rats. In streptozotocin-induced diabetic rats, the expression levels of TRPV4 and K(Ca)2.3 were reduced, which could be an underlying reason for the dysfunction of endothelium-dependent hyperpolarization in these animals. These results demonstrated an important physiological and pathological role of TRPV4-K(Ca)2.3 signaling pathway in vascular endothelial cells.