Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/36283
Title: No evidence for altered intracellular calcium-handling in airway smooth muscle cells from human subjects with asthma
Authors: Sweeney, David
Hollins, Fay
Gomez, Edith
Mistry, Rajendra
Saunders, Ruth Mary
Challiss, Robert A. J.
Brightling, Christopher E.
First Published: 13-Feb-2015
Publisher: BioMed Central
Citation: BMC Pulmonary Medicine, 2015, 15 : 12
Abstract: Background: Asthma is characterized by airway hyper-responsiveness and variable airflow obstruction, in part as a consequence of hyper-contractile airway smooth muscle, which persists in primary cell culture. One potential mechanism for this hyper-contractility is abnormal intracellular Ca2+ handling. Methods: We sought to compare intracellular Ca2+ handling in airway smooth muscle cells from subjects with asthma compared to non-asthmatic controls by measuring: i) bradykinin-stimulated changes in inositol 1,4,5-trisphosphate (IP3) accumulation and intracellular Ca2+ concentration, ii) sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) expression, iii) mechanisms of cytoplasmic Ca2+ clearance assessed following instantaneous flash photolytic release of Ca2+ into the cytoplasm. Results: We found no differences in airway smooth muscle cell basal intracellular Ca2+ concentrations, bradykinin-stimulated IP3 accumulation or intracellular Ca2+ responses. Quantification of SERCA2 mRNA or protein expression levels revealed no differences in ASM cells obtained from subjects with asthma compared to non-asthmatic controls. We did not identify differences in intracellular calcium kinetics assessed by flash photolysis and calcium uncaging independent of agonist-activation with or without SERCA inhibition. However, we did observe some correlations in subjects with asthma between lung function and the different cellular measurements of intracellular Ca2+ handling, with poorer lung function related to increased rate of recovery following flash photolytic elevation of cytoplasmic Ca2+ concentration. Conclusions: Taken together, the experimental results reported in this study do not demonstrate major fundamental differences in Ca2+ handling between airway smooth muscle cells from non-asthmatic and asthmatic subjects. Therefore, increased contraction of airway smooth muscle cells derived from asthmatic subjects cannot be fully explained by altered Ca2+ homeostasis.
DOI Link: 10.1186/s12890-015-0009-z
eISSN: 1471-2466
Links: http://bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-015-0009-z
http://hdl.handle.net/2381/36283
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © Sweeney et al.; licensee BioMed Central. 2015 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.
Description: PMCID: PMC4342789
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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