Functional Role of TRPV4-KCa2.3 Signaling in Vascular Endothelial Cells in Normal and Streptozotocin-Induced Diabetic Rats

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2013-07, Vol.62 (1), p.134-139
• Main Authors: Ma, Xin, Du, Juan, Zhang, Peng, Deng, Jianxin, Liu, Jie, Lam, Francis Fu-Yuen, Li, Ronald A, Huang, Yu, Jin, Jian, Yao, Xiaoqiang
• Format: Article
• Language: English
• Subjects: Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Flow Velocity; Cardiology. Vascular system; Cells, Cultured; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - pathology; Diabetes Mellitus, Experimental - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelial Cells - metabolism; Endothelial Cells - pathology; Endothelium, Vascular - metabolism; Endothelium, Vascular - physiopathology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Immunoblotting; Intermediate-Conductance Calcium-Activated Potassium Channels - metabolism; Male; Medical sciences; Mesenteric Arteries - metabolism; Mesenteric Arteries - physiopathology; Osmotic Pressure; Rats; Rats, Sprague-Dawley; Signal Transduction; Streptozocin - toxicity; TRPV Cation Channels - metabolism; Vascular Resistance - physiology; Vasodilation - physiology
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.113.01500

The small conductance and intermediate conductance Ca-activated K channels are known to be involved in the endothelium-dependent hyperpolarization. Ca 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 KCa2.3 in rat mesenteric artery endothelial cells. Acetylcholine and 4α-PDD mainly acted through TRPV4-KCa2.3 pathway to induce smooth muscle hyperpolarization and vascular relaxation. KCa3.1 was also involved in the process but at a much lesser degree than that of KCa2.3. Stimulating TRPV4-KCa2.3 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 KCa2.3 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-KCa2.3 signaling pathway in vascular endothelial cells.