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dc.contributor.authorDuffy, S Marken
dc.contributor.authorAshmole, I.en
dc.contributor.authorSmallwood, Dawn T.en
dc.contributor.authorLeyland, Mark L.en
dc.contributor.authorBradding, Peteren
dc.date.accessioned2017-10-30T11:46:27Z
dc.date.available2017-10-30T11:46:27Z
dc.date.issued2015-07-16
dc.identifier.citationDuffy, S,M., Ashmole, I., Smallwood, D.T., Leyland, M.L and Bradding, P. (2015) Orai/CRACM1 and KCa3.1 ion channels interact in the human lung mast cell plasma membrane. Cell Communication and Signaling, 13:32en
dc.identifier.urihttp://hdl.handle.net/2086/14734
dc.descriptionopen access articleen
dc.description.abstractBACKGROUND: Orai/CRACM1 ion channels provide the major Ca(2+) influx pathway for FcεRI-dependent human lung mast cell (HLMC) mediator release. The Ca(2+)-activated K(+) channel KCa3.1 modulates Ca(2+) influx and the secretory response through hyperpolarisation of the plasma membrane. We hypothesised that there is a close functional and spatiotemporal interaction between these Ca(2+)- and K(+)-selective channels. RESULTS: Activation of FcεRI-dependent HLMC KCa3.1 currents was dependent on the presence of extracellular Ca(2+), and attenuated in the presence of the selective Orai blocker GSK-7975A. Currents elicited by the KCa3.1 opener 1-EBIO were also attenuated by GSK-7975A. The Orai1 E106Q dominant-negative mutant ablated 1-EBIO and FcεRI-dependent KCa3.1 currents in HLMCs. Orai1 but not Orai2 was shown to co-immunoprecipitate with KCa3.1 when overexpressed in HEK293 cells, and Orai1 and KCa3.1 were seen to co-localise in the HEK293 plasma membrane using confocal microscopy. CONCLUSION: KCa3.1 activation in HLMCs is highly dependent on Ca(2+) influx through Orai1 channels, mediated via a close spatiotemporal interaction between the two channels.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.subjectOrai/CRACMen
dc.subjectKCa3.1en
dc.subjecthuman lung mast cellen
dc.titleOrai/CRACM1 and KCa3.1 ion channels interacten
dc.typeArticleen
dc.identifier.doihttps://dx.doi.org/10.1186/s12964-015-0112-z
dc.peerreviewedYesen
dc.explorer.multimediaNoen
dc.funderWellcome Trust UK, National Institute for Health Research Leicester Respiratory Biomedical Research Uniten
dc.projectidWellcome Trust 087499en
dc.cclicenceCC-BY-NCen
dc.date.acceptance2015-07-09en
dc.exception.reasonopen access articleen
dc.researchinstituteInstitute for Allied Health Sciences Researchen


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