Mathematical Modelling of Ca2+ Oscillations in Airway Smooth Muscle Cells

Brumen, Milan; Fajmut, Aleš; Dobovišek, Andrej; Roux, Étienne

doi:10.1007/s10867-005-2409-4

Cited by 7 publications

(6 citation statements)

References 19 publications

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“…Brumen et al . studied the influence of the total content on the nature (damped or sustained) and frequency of agonist-induced oscillations [21]. Roux et al did not model oscillations, but transient responses to caffeine [20].…”

Section: Discussionmentioning

confidence: 99%

Activation of Store-Operated Calcium Entry in Airway Smooth Muscle Cells: Insight from a Mathematical Model

et al. 2013

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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.

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Section: Discussionmentioning

confidence: 99%

Activation of Store-Operated Calcium Entry in Airway Smooth Muscle Cells: Insight from a Mathematical Model

et al. 2013

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“…What mechanisms underlie airway peristalsis is not clear. In adult ASM (and in other smooth muscle cell types), baseline [Ca 2ϩ ] i oscillations modulated by agonist stimulation have now been shown extensively (70,223,406,425,459,521). Many of the [Ca 2ϩ ] i regulatory pathways involved in adult ASM are also present in developing ASM (206) and could play a role.…”

Section: Asm In Airway Developmentmentioning

confidence: 99%

Emerging concepts in smooth muscle contributions to airway structure and function: implications for health and disease

Prakash

2016

American Journal of Physiology-Lung Cellular and Molecular Phys

114

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Airway structure and function are key aspects of normal lung development, growth, and aging, as well as of lung responses to the environment and the pathophysiology of important diseases such as asthma, chronic obstructive pulmonary disease, and fibrosis. In this regard, the contributions of airway smooth muscle (ASM) are both functional, in the context of airway contractility and relaxation, as well as synthetic, involving production and modulation of extracellular components, modulation of the local immune environment, cellular contribution to airway structure, and, finally, interactions with other airway cell types such as epithelium, fibroblasts, and nerves. These ASM contributions are now found to be critical in airway hyperresponsiveness and remodeling that occur in lung diseases. This review emphasizes established and recent discoveries that underline the central role of ASM and sets the stage for future research toward understanding how ASM plays a central role by being both upstream and downstream in the many interactive processes that determine airway structure and function in health and disease.

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“…Deterministic models of the have proven to be useful predictive models in a range of cell types. For example, -based models have been developed to study oscillations in airway smooth muscle cells (ASMC) [10] – [13] , and these models have made predictions which have been confirmed experimentally. This shows the usefulness of such models in advancing our understanding of how intracellular oscillations and waves are initiated and controlled in ASMC.…”

Section: Introductionmentioning

confidence: 99%

A Deterministic Model Predicts the Properties of Stochastic Calcium Oscillations in Airway Smooth Muscle Cells

et al. 2014

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The inositol trisphosphate receptor () is one of the most important cellular components responsible for oscillations in the cytoplasmic calcium concentration. Over the past decade, two major questions about the have arisen. Firstly, how best should the be modeled? In other words, what fundamental properties of the allow it to perform its function, and what are their quantitative properties? Secondly, although calcium oscillations are caused by the stochastic opening and closing of small numbers of , is it possible for a deterministic model to be a reliable predictor of calcium behavior? Here, we answer these two questions, using airway smooth muscle cells (ASMC) as a specific example. Firstly, we show that periodic calcium waves in ASMC, as well as the statistics of calcium puffs in other cell types, can be quantitatively reproduced by a two-state model of the , and thus the behavior of the is essentially determined by its modal structure. The structure within each mode is irrelevant for function. Secondly, we show that, although calcium waves in ASMC are generated by a stochastic mechanism, stochasticity is not essential for a qualitative prediction of how oscillation frequency depends on model parameters, and thus deterministic models demonstrate the same level of predictive capability as do stochastic models. We conclude that, firstly, calcium dynamics can be accurately modeled using simplified models, and, secondly, to obtain qualitative predictions of how oscillation frequency depends on parameters it is sufficient to use a deterministic model.

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Mathematical Modelling of Ca2+ Oscillations in Airway Smooth Muscle Cells

Cited by 7 publications

References 19 publications

Activation of Store-Operated Calcium Entry in Airway Smooth Muscle Cells: Insight from a Mathematical Model

Activation of Store-Operated Calcium Entry in Airway Smooth Muscle Cells: Insight from a Mathematical Model

Emerging concepts in smooth muscle contributions to airway structure and function: implications for health and disease

A Deterministic Model Predicts the Properties of Stochastic Calcium Oscillations in Airway Smooth Muscle Cells

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