title: Functional role of TRPV4-KCa2.3 signaling in vascular endothelial cells in normal and streptozotocin-induced diabetic rats.
abstract: The small conductance and intermediate conductance Ca(2+)-activated K(+) channels are known to be involved in the endothelium-dependent hyperpolarization. Ca(2+) 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 4α-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.
authors: School of Medicine and Pharmaceutics, Jiangnan University, Wuxi, China.
authors: Xin
authors: X
authors: Ma
authors: Juan
authors: J
authors: Du
authors: Peng
authors: P
authors: Zhang
authors: Jianxin
authors: J
authors: Deng
authors: Jie
authors: J
authors: Liu
authors: Francis Fu-Yuen
authors: FF
authors: Lam
authors: Ronald A
authors: RA
authors: Li
authors: Yu
authors: Y
authors: Huang
authors: Jian
authors: J
authors: Jin
authors: Xiaoqiang
authors: X
authors: Yao
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D015151:Immunoblotting; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism / Q000503:physiopathology*; D009997:Osmotic Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013311:Streptozocin / Q000633:toxicity; D050916:TRPV Cation Channels / Q000378:metabolism*; D014655:Vascular Resistance / Q000502:physiology; D014664:Vasodilation / Q000502:physiology*
chemical_list: D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D050916:TRPV Cation Channels; C486577:Trpv4 protein, rat; D013311:Streptozocin
keywords: TRPV4-KCa2.3 association; endothelial cells; endothelium-derived hyperpolarizing factor; vascular relaxation