Functional TRPC5‐containing channels in human saphenous vein endothelial cells

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Vascular endothelium plays pivotal roles in regulation of vascular tone, blood coagulation, wound healing and cell‐cell adhesion via the expression of vasoactive mediators. Ca2+ plays a central role in the regulation of endothelial cell function. Classical transient receptor potential channels (TRPC1‐7) are widely expressed and some are suggested to play critical roles in regulating endothelial functions. Here, we demonstrate the expression and functionality of TRPC5‐containing channels in human saphenous vein endothelial cells (HSVEC). RT‐PCR analysis suggested that TRPC1, 4, and 5 are expressed in HSVEC. Cells were then studied using fura‐2 real‐time 96‐well plate assays. Challenging of HSVEC with 10 µM histamine or lysophosphatidylcholine (LPC), 1 mM H2O2 or 100 ng/mL vascular endothelial growth factor (VEGF) induced rises in [Ca2+ ]i, which was inhibited by a TRPC5‐specific polyclonal antibody. The inhibition varied from ~80% in the case of LPC, to ~40, 50 and 70% for the histamine, H2O2 and VEGF responses. ATP (100 µM) mediated Ca2+ rise was not affected. Our data support earlier murine studies, and suggest the involvement of TRPC5‐containing channels in mediating Ca2+ signals in human endothelial cells. The channel may be important in inflammatory, oxidative or angiogenic conditions, and is a potential target for therapeutic development.Work supported by the Wellcome Trust and The Egyptian Ministry of Higher Education.Grant Funding SourceWellcome Trust and Egyptian Ministry of Higher Education