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Towards a predictive model of Ca²⁺ puffs

Thul, Ruediger; Thurley, Kevin; Falcke, Martin

Authors

Kevin Thurley

Martin Falcke



Abstract

We investigate key characteristics of Ca²⁺ puffs in deterministic and stochastic frameworks that all incorporate the cellular morphology of IP[subscript]3 receptor channel clusters. In a first step, we numerically study Ca²⁺ liberation in a three dimensional representation of a cluster environment with reaction-diffusion dynamics in both the cytosol and the lumen. These simulations reveal that Ca²⁺ concentrations at a releasing cluster range from 80 µM to 170 µM and equilibrate almost instantaneously on the time scale of the release duration. These highly elevated Ca²⁺ concentrations eliminate Ca²⁺ oscillations in a deterministic model of an IP[subscript]3R channel cluster at physiological parameter values as revealed by a linear stability analysis. The reason lies in the saturation of all feedback processes in the IP[subscript]3R gating dynamics, so that only fluctuations can restore experimentally observed Ca²⁺ oscillations. In this spirit, we derive master equations that allow us to analytically quantify the onset of Ca²⁺ puffs and hence the stochastic time scale of intracellular Ca²⁺ dynamics. Moving up the spatial scale, we suggest to formulate cellular dynamics in terms of waiting time distribution functions. This approach prevents the state space explosion that is typical for the description of cellular dynamics based on channel states and still contains information on molecular fluctuations. We illustrate this method by studying global Ca²⁺ oscillations.

Citation

Thul, R., Thurley, K., & Falcke, M. (2009). Towards a predictive model of Ca²⁺ puffs. Chaos, 19, doi:10.1063/1.3183809

Journal Article Type Article
Publication Date Jan 1, 2009
Deposit Date Sep 22, 2009
Publicly Available Date Sep 22, 2009
Journal Chaos
Print ISSN 1054-1500
Electronic ISSN 1054-1500
Publisher AIP Publishing
Peer Reviewed Peer Reviewed
Volume 19
DOI https://doi.org/10.1063/1.3183809
Public URL http://eprints.nottingham.ac.uk/id/eprint/1131
Publisher URL http://link.aip.org/link/?CHAOEH/19/037108/1
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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