- PLoS One
- v.8(7); 2013
- PMC3723852
PLoS One. 2013; 8(7): e69598.
Published online 2013 July 25. doi: 10.1371/journal.pone.0069598
PMCID: PMC3723852
Activation of Store-Operated Calcium Entry in Airway Smooth Muscle Cells: Insight from a Mathematical Model
Laszlo Csernoch, Editor
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.
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.
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