Flegg, M. B. and Rudiger, S and Erban, R. (2013) Diffusive spatiotemporal noise in a firstpassage time model for intracellular calcium release. Journal of Chemical Physics, 138 (15). p. 154103.

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Abstract
The intracellular release of calcium from the endoplasmic reticulum is controlled by ion channels. The resulting calcium signals exhibit a rich spatiotemporal signature, which originates at least partly from microscopic fluctuations. While stochasticity in the gating transition of ion channels has been incorporated into many models, the distribution of calcium is usually described by deterministic reactiondiffusion equations. Here we test the validity of the latter modeling approach by using two different models to calculate the frequency of localized calcium signals (calcium puffs) from clustered IP3 receptor channels. The complexity of the full calcium system is here limited to the basic opening mechanism of the ion channels and, in the mathematical reduction simplifies to the calculation of a first passage time. Two models are then studied: (i) a hybrid model, where channel gating is treated stochastically, while calcium concentration is deterministic and (ii) a fully stochastic model with noisy channel gating and Brownian calcium ion motion. The second model utilises the recently developed tworegime method [M. B. Flegg, S. J. Chapman, and R. Erban, “The tworegime method for optimizing stochastic reactiondiffusion simulations,” J. R. Soc., Interface9, 859–868 (Year: 2012)]10.1098/rsif.2011.0574 in order to simulate a large domain with precision required only near the Ca2+ absorbing channels. The expected time for a first channel opening that results in a calcium puff event is calculated. It is found that for a large diffusion constant, predictions of the interpuff time are significantly overestimated using the model (i) with a deterministic nonspatial calcium variable. It is thus demonstrated that the presence of diffusive noise in local concentrations of intracellular Ca2+ ions can substantially influence the occurrence of calcium signals. The presented approach and results may also be relevant for other cellphysiological firstpassage time problems with small ligand concentration and high cooperativity.
Item Type:  Article 

Subjects:  A  C > Biology and other natural sciences 
Research Groups:  Centre for Mathematical Biology 
ID Code:  1782 
Deposited By:  Sara Jolliffe 
Deposited On:  13 Feb 2014 08:46 
Last Modified:  29 May 2015 19:28 
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