Activation of store-operated calcium entry in airway smooth muscle cells: insight from a mathematical model
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 mathematic...
| Main Authors: | , , , , , |
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| Format: | Article |
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Public Library of Science
2013
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| Online Access: | https://eprints.nottingham.ac.uk/2584/ |
| _version_ | 1848790823167066112 |
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| author | Croisier, Huguette Tan, Xiahui Perez-Zoghbi, Jose F. Sanderson, Michael J. Sneyd, James Brook, Bindi S. |
| author_facet | Croisier, Huguette Tan, Xiahui Perez-Zoghbi, Jose F. Sanderson, Michael J. Sneyd, James Brook, Bindi S. |
| author_sort | Croisier, Huguette |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T18:18:44Z |
| format | Article |
| id | nottingham-2584 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T18:18:44Z |
| publishDate | 2013 |
| publisher | Public Library of Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-25842020-05-04T16:37:45Z https://eprints.nottingham.ac.uk/2584/ 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. 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. Public Library of Science 2013-07-25 Article PeerReviewed Croisier, Huguette, Tan, Xiahui, Perez-Zoghbi, Jose F., Sanderson, Michael J., 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 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0069598 doi:10.1371/journal.pone.0069598 doi:10.1371/journal.pone.0069598 |
| spellingShingle | Croisier, Huguette Tan, Xiahui Perez-Zoghbi, Jose F. Sanderson, Michael J. Sneyd, James Brook, Bindi S. Activation of store-operated calcium entry in airway smooth muscle cells: insight from a mathematical model |
| title | Activation of store-operated calcium entry in airway
smooth muscle cells: insight from a mathematical model |
| title_full | Activation of store-operated calcium entry in airway
smooth muscle cells: insight from a mathematical model |
| title_fullStr | Activation of store-operated calcium entry in airway
smooth muscle cells: insight from a mathematical model |
| title_full_unstemmed | Activation of store-operated calcium entry in airway
smooth muscle cells: insight from a mathematical model |
| title_short | Activation of store-operated calcium entry in airway
smooth muscle cells: insight from a mathematical model |
| title_sort | activation of store-operated calcium entry in airway
smooth muscle cells: insight from a mathematical model |
| url | https://eprints.nottingham.ac.uk/2584/ https://eprints.nottingham.ac.uk/2584/ https://eprints.nottingham.ac.uk/2584/ |