Heteromeric TRPV4-C1 channels contribute to store-operated Ca(2+) entry in vascular endothelial cells |
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Authors: | Ma Xin Cheng Kwong-Tai Wong Ching-On O'Neil Roger G Birnbaumer Lutz Ambudkar Indu S Yao Xiaoqiang |
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Affiliation: | aSchool of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, China;bLi Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China;cMolecular Physiology and Therapeutics Branch, NIDCR, National Institutes of Health, Bethesda, MD, USA;dDepartment of Integrative Biology and Pharmacology, The University of Texas Health Science Center, Houston, TX, USA;eLaboratory of Neurobiology, National Institute of Environmental Sciences, Research Triangle Park, NC 27709, USA |
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Abstract: | There is controversy as to whether TRP channels participate in mediating store-operated current (ISOC) and store-operated Ca2+ entry (SOCE). Our recent study has demonstrated that TRPC1 forms heteromeric channels with TRPV4 in vascular endothelial cells and that Ca2+ store depletion enhances the vesicle trafficking of heteromeric TRPV4-C1 channels, causing insertion of more channels into the plasma membrane in vascular endothelial cells. In the present study, we determined whether the enhanced TRPV4-C1 insertion to the plasma membrane could contribute to SOCE and ISOC. We found that thapsigargin-induced SOCE was much lower in aortic endothelial cells derived from trpv4−/− or trpc1−/− knockout mice when compared to that of wild-type mice. In human umbilical vein endothelial cells (HUVECs), thapsigargin-induced SOCE was markedly reduced by knocking down the expression of TRPC1 and/or TRPV4 with respective siRNAs. Brefeldin A, a blocker of vesicular translocation, inhibited the SOCE. These results suggest that an enhanced vesicular trafficking of heteromeric TRPV4-C1 channels contributes to SOCE in vascular endothelial cells. Vascular tension studies suggest that such an enhanced trafficking of TRPV4-C1 channels may play a role in thapsigargin-induced vascular relaxation in rat small mesenteric arteries. |
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Keywords: | Abbreviations: TRP, transient receptor potential ISOC, store-operated current SOCE, store-operated Ca2+ entry STIM1, stromal interacting molecule 1 HUVEC, human umbilical vein endothelial cells NPSS, normal physiological saline solution |
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