Towards a predictive model of Ca²⁺ puffs
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 w...
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| Format: | Article |
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American Institute of Physics
2009
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| Online Access: | https://eprints.nottingham.ac.uk/1131/ |
| _version_ | 1848790542512553984 |
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| author | Thul, Ruediger Thurley, Kevin Falcke, Martin |
| author_facet | Thul, Ruediger Thurley, Kevin Falcke, Martin |
| author_sort | Thul, Ruediger |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T18:14:16Z |
| format | Article |
| id | nottingham-1131 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T18:14:16Z |
| publishDate | 2009 |
| publisher | American Institute of Physics |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-11312020-05-04T20:27:06Z https://eprints.nottingham.ac.uk/1131/ Towards a predictive model of Ca²⁺ puffs Thul, Ruediger Thurley, Kevin Falcke, Martin 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. American Institute of Physics 2009 Article PeerReviewed Thul, Ruediger, Thurley, Kevin and Falcke, Martin (2009) Towards a predictive model of Ca²⁺ puffs. Chaos, 19 . 037108. ISSN 1054-1500 http://link.aip.org/link/?CHAOEH/19/037108/1 10.1063/1.3183809 10.1063/1.3183809 10.1063/1.3183809 |
| spellingShingle | Thul, Ruediger Thurley, Kevin Falcke, Martin Towards a predictive model of Ca²⁺ puffs |
| title | Towards a predictive model of Ca²⁺ puffs |
| title_full | Towards a predictive model of Ca²⁺ puffs |
| title_fullStr | Towards a predictive model of Ca²⁺ puffs |
| title_full_unstemmed | Towards a predictive model of Ca²⁺ puffs |
| title_short | Towards a predictive model of Ca²⁺ puffs |
| title_sort | towards a predictive model of ca²⁺ puffs |
| url | https://eprints.nottingham.ac.uk/1131/ https://eprints.nottingham.ac.uk/1131/ https://eprints.nottingham.ac.uk/1131/ |