Show simple item record

dc.contributor.authorShi, Jianen_US
dc.contributor.authorMiralles, Francescen_US
dc.contributor.authorKinet, Jean-Pierreen_US
dc.contributor.authorBirnbaumer, Lutzen_US
dc.contributor.authorLarge, William A.en_US
dc.contributor.authorAlbert, Anthony P.en_US
dc.date.accessioned2017-12-05T23:48:15Z
dc.date.issued2017en_US
dc.identifier.citationShi, Jian, Francesc Miralles, Jean-Pierre Kinet, Lutz Birnbaumer, William A. Large, and Anthony P. Albert. 2017. “Evidence that Orai1 does not contribute to store-operated TRPC1 channels in vascular smooth muscle cells.” Channels 11 (4): 329-339. doi:10.1080/19336950.2017.1303025. http://dx.doi.org/10.1080/19336950.2017.1303025.en
dc.identifier.issnen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:34491889
dc.description.abstractABSTRACT Ca2+-permeable store-operated channels (SOCs) mediate Ca2+ entry pathways which are involved in many cellular functions such as contraction, growth, and proliferation. Prototypical SOCs are formed of Orai1 proteins and are activated by the endo/sarcoplasmic reticulum Ca2+ sensor stromal interaction molecule 1 (STIM1). There is considerable debate about whether canonical transient receptor potential 1 (TRPC1) proteins also form store-operated channels (SOCs), and if they do, is Orai1 involved. We recently showed that stimulation of TRPC1-based SOCs involves store depletion inducing STIM1-evoked Gαq/PLCβ1 activity in contractile vascular smooth muscle cells (VSMCs). Therefore the present work investigates the role of Orai1 in activation of TRPC1-based SOCs in freshly isolated mesenteric artery VSMCs from wild-type (WT) and Orai1−/− mice. Store-operated whole-cell and single channel currents recorded from WT and Orai1−/− VSMCs had similar properties, with relatively linear current-voltage relationships, reversal potentials of about +20mV, unitary conductances of about 2pS, and inhibition by anti-TRPC1 and anti-STIM1 antibodies. In Orai1−/− VSMCs, store depletion induced PLCβ1 activity measured with the fluorescent phosphatidylinositol 4,5-bisphosphate/inositol 1,4,5-trisphosphate biosensor GFP-PLCδ1-PH, which was prevented by knockdown of STIM1. In addition, in Orai1−/− VSMCs, store depletion induced translocation of STIM1 from within the cell to the plasma membrane where it formed STIM1-TRPC1 interactions at discrete puncta-like sites. These findings indicate that activation of TRPC1-based SOCs through a STIM1-activated PLCβ1 pathway are likely to occur independently of Orai1 proteins, providing evidence that TRPC1 channels form genuine SOCs in VSMCs with a contractile phenotype.en
dc.language.isoen_USen
dc.publisherTaylor & Francisen
dc.relation.isversionofdoi:10.1080/19336950.2017.1303025en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555289/pdf/en
dash.licenseLAAen_US
dc.subjectOrai1en
dc.subjectPLCen
dc.subjectSTIM1en
dc.subjectstore-operateden
dc.subjectTRPC1en
dc.subjectvascular smooth muscleen
dc.titleEvidence that Orai1 does not contribute to store-operated TRPC1 channels in vascular smooth muscle cellsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalChannelsen
dash.depositing.authorKinet, Jean-Pierreen_US
dc.date.available2017-12-05T23:48:15Z
dc.identifier.doi10.1080/19336950.2017.1303025*
dash.contributor.affiliatedKinet, Jean-Pierre


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record