title: Heteromeric TRPV4-C1 channels contribute to store-operated Ca(2+) entry in vascular endothelial cells.
abstract: There is controversy as to whether TRP channels participate in mediating store-operated current (I(SOC)) and store-operated Ca(2+) entry (SOCE). Our recent study has demonstrated that TRPC1 forms heteromeric channels with TRPV4 in vascular endothelial cells and that Ca(2+) 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 I(SOC). 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.
authors.affiliation: School of Biomedical Sciences, Chinese University of Hong Kong.
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.forename: Kwong-Tai
authors.initials: KT
authors.lastname: Cheng
authors.forename: Ching-On
authors.initials: CO
authors.lastname: Wong
authors.forename: Roger G
authors.initials: RG
authors.lastname: O'Neil
authors.forename: Lutz
authors.initials: L
authors.lastname: Birnbaumer
authors.forename: Indu S
authors.initials: IS
authors.lastname: Ambudkar
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Yao
mesh_terms: D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D016257:Fura-2; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D009154:Mutation; D018408:Patch-Clamp Techniques; D034741:RNA, Small Interfering; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D034741:RNA, Small Interfering; D050052:TRPC Cation Channels; D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse; C096351:transient receptor potential cation channel, subfamily C, member 1; D020126:Brefeldin A; D019284:Thapsigargin; D002118:Calcium; D016257:Fura-2