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|Title:||KCa3.1 K+ Channel Expression and Function in Human Bronchial Epithelial Cells|
|Authors:||Arthur, Greer K.|
Duffy, S. Mark
Roach, Katy M.
Hirst, Rob A.
Gaillard, Erol A.
|Publisher:||Public Library of Science|
|Citation:||PLoS One, 2015, 10 (12), e0145259|
|Abstract:||The KCa3.1 K+ channel has been proposed as a novel target for pulmonary diseases such as asthma and pulmonary fibrosis. It is expressed in epithelia but its expression and function in primary human bronchial epithelial cells (HBECs) has not been described. Due to its proposed roles in the regulation of cell proliferation, migration, and epithelial fluid secretion, inhibiting this channel might have either beneficial or adverse effects on HBEC function. The aim of this study was to assess whether primary HBECs express the KCa3.1 channel and its role in HBEC function. Primary HBECs from the airways of healthy and asthmatic subjects, SV-transformed BEAS-2B cells and the neoplastic H292 epithelial cell line were studied. Primary HBECs, BEAS-2B and H292 cells expressed KCa3.1 mRNA and protein, and robust KCa3.1 ion currents. KCa3.1 protein expression was increased in asthmatic compared to healthy airway epithelium in situ, and KCa3.1 currents were larger in asthmatic compared to healthy HBECs cultured in vitro. Selective KCa3.1 blockers (TRAM-34, ICA-17043) had no effect on epithelial cell proliferation, wound closure, ciliary beat frequency, or mucus secretion. However, several features of TGFβ1-dependent epithelial-mesenchymal transition (EMT) were inhibited by KCa3.1 blockade. Treatment with KCa3.1 blockers is likely to be safe with respect to airway epithelial biology, and may potentially inhibit airway remodelling through the inhibition of EMT.|
|Rights:||Copyright © 2015 Arthur 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 author and source are credited|
|Appears in Collections:||Published Articles, Dept. of Infection, Immunity and Inflammation|
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|KCa3.1 K+ Channel Expression and Function in Human Bronchial Epithelial Cells..pdf||Published (publisher PDF)||874.27 kB||Adobe PDF||View/Open|
|PONE-D-15-39638R3_FTC PB.pdf||Post-review (final submitted)||214.4 kB||Adobe PDF||View/Open|
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