Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/32842
Title: Orai/CRACM1 and KCa3.1 ion channels interact in the human lung mast cell plasma membrane
Authors: Duffy, S. Mark
Ashmole, Ian
Smallwood, Dawn T.
Leyland, Mark L.
Bradding, Peter
First Published: 16-Jul-2015
Publisher: BioMed Central
Citation: Cell Communication and Signaling, 2015, 13 (1), 32
Abstract: BACKGROUND: Orai/CRACM1 ion channels provide the major Ca[superscript: 2+] influx pathway for FcεRI-dependent human lung mast cell (HLMC) mediator release. The Ca[superscript: 2+]-activated K[superscript: +] channel K[subscript: Ca]3.1 modulates Ca[superscript: 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[superscript: 2+]- and K[superscript: +]-selective channels. RESULTS: Activation of FcεRI-dependent HLMC K[subscript: Ca]3.1 currents was dependent on the presence of extracellular Ca[superscript: 2+], and attenuated in the presence of the selective Orai blocker GSK-7975A. Currents elicited by the K[subscript: Ca]3.1 opener 1-EBIO were also attenuated by GSK-7975A. The Orai1 E106Q dominant-negative mutant ablated 1-EBIO and FcεRI-dependent K[subscript: Ca]3.1 currents in HLMCs. Orai1 but not Orai2 was shown to co-immunoprecipitate with K[subscript: Ca]3.1 when overexpressed in HEK293 cells, and Orai1 and K[subscript: Ca]3.1 were seen to co-localise in the HEK293 plasma membrane using confocal microscopy. CONCLUSION: K[subscript: Ca]3.1 activation in HLMCs is highly dependent on Ca[superscript: 2+] influx through Orai1 channels, mediated via a close spatiotemporal interaction between the two channels.
DOI Link: 10.1186/s12964-015-0112-z
eISSN: 1478-811X
Links: http://www.biosignaling.com/content/13/1/32
http://hdl.handle.net/2381/32842
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2015 Duffy et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

Files in This Item:
File Description SizeFormat 
Published pdf.pdfPublished (publisher PDF)1.85 MBAdobe PDFView/Open


Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.