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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Main Authors: Thul, Ruediger, Thurley, Kevin, Falcke, Martin
Format: Article
Published: American Institute of Physics 2009
Online Access:https://eprints.nottingham.ac.uk/1131/
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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.
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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/