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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
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 (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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