Department of Microbiology and Physiological Systems
Biostatistics | Cellular and Molecular Physiology | Computational Biology | Statistical Models
The inositol trisphosphate receptor ([Formula: see text]) 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 [Formula: see text] have arisen. Firstly, how best should the [Formula: see text] be modeled? In other words, what fundamental properties of the [Formula: see text] 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 [Formula: see text], 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 [Formula: see text], and thus the behavior of the [Formula: see text] 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, [Formula: see text] stochasticity is not essential for a qualitative prediction of how oscillation frequency depends on model parameters, and thus deterministic [Formula: see text] models demonstrate the same level of predictive capability as do stochastic models. We conclude that, firstly, calcium dynamics can be accurately modeled using simplified [Formula: see text] 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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Citation: PLoS Comput Biol. 2014 Aug 14;10(8):e1003783. doi: 10.1371/journal.pcbi.1003783. eCollection 2014. Link to article on publisher's site
DOI of Published Version
PLoS computational biology
Cao, Pengxing; Tan, Xiahui; Donovan, Graham; Sanderson, Michael J.; and Sneyd, James, "A deterministic model predicts the properties of stochastic calcium oscillations in airway smooth muscle cells" (2014). Open Access Articles. 2463.
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