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

Croisier, Huguette; Tan, Xiahui; Perez-Zoghbi, Jose F.; Sanderson, Michael J.; Sneyd, James; Brook, Bindi S.

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.

Citation

Croisier, H., Tan, X., Perez-Zoghbi, J. F., Sanderson, M. J., Sneyd, J., & Brook, B. S. (2013). Activation of store-operated calcium entry in airway smooth muscle cells: insight from a mathematical model. PLoS ONE, 8(7), Article e69598. https://doi.org/10.1371/journal.pone.0069598

• Journal Article Type: Article
• Publication Date: Jul 25, 2013
• Deposit Date: Mar 25, 2014
• Publicly Available Date: Mar 25, 2014
• Journal: PLoS ONE
• Electronic ISSN: 1932-6203
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 7
• Article Number: e69598
• DOI: https://doi.org/10.1371/journal.pone.0069598
• Public URL: https://nottingham-repository.worktribe.com/output/716156
• Publisher URL: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0069598