Activation of store-operated calcium entry in airway smooth muscle cells: insight from a mathematical model

Croisier, Huguette and Tan, Xiahui and Perez-Zoghbi, Jose F. and Sanderson, Michael J. and Sneyd, James and Brook, Bindi S. (2013) Activation of store-operated calcium entry in airway smooth muscle cells: insight from a mathematical model. PLoS ONE, 8 (7). e69598/1-e69598/11. ISSN 1932-6203

[img] PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Available under Licence Creative Commons Attribution.
Download (2MB)

Abstract

Intracellular dynamics of airway smooth muscle cells (ASMC) mediate ASMC contraction and proliferation, and thus play a key role in airway hyper-responsiveness (AHR) and remodelling in asthma. We evaluate the importance of store-operated entry (SOCE) in these dynamics by constructing a mathematical model of ASMC signaling based on experimental data from lung slices. The model confirms that SOCE is elicited upon sufficient depletion of the sarcoplasmic reticulum (SR), while receptor-operated entry (ROCE) is inhibited in such conditions. It also shows that SOCE can sustain agonist-induced oscillations in the absence of other influx. SOCE up-regulation may thus contribute to AHR by increasing the oscillation frequency that in turn regulates ASMC contraction. The model also provides an explanation for the failure of the SERCA pump blocker CPA to clamp the cytosolic of ASMC in lung slices, by showing that CPA is unable to maintain the SR empty of . This prediction is confirmed by experimental data from mouse lung slices, and strongly suggests that CPA only partially inhibits SERCA in ASMC.

Item Type: Article
Schools/Departments: University of Nottingham UK Campus > Faculty of Science > School of Mathematical Sciences
Depositing User: Snowden, Ms Diane
Date Deposited: 25 Mar 2014 10:29
Last Modified: 13 Sep 2016 15:13
URI: http://eprints.nottingham.ac.uk/id/eprint/2584

Actions (Archive Staff Only)

Edit View Edit View