Receptors, sparks and waves in a fire-diffuse-fire framework for calcium release

Coombes, Stephen; Hinch, Robert; Timofeeva, Yulia

Abstract

Calcium ions are an important second messenger in living cells. Indeed calcium signals in the form of waves have been the subject of much recent experimental interest. It is now well established that these waves are composed of elementary stochastic release events (calcium puffs or sparks) from spatially localised calcium stores. The aim of this paper is to analyse how the stochastic nature of individual receptors within these stores combines to create stochastic behaviour on long timescales that may ultimately lead to waves of activity in a spatially extended cell model. Techniques from asymptotic analysis and stochastic phase-plane analysis are used to show that a large cluster of receptor channels leads to a release probability with a sigmoidal dependence on calcium density. This release probability is incorporated into a computationally inexpensive model of calcium release based upon a stochastic generalization of the Fire-Diffuse-Fire (FDF) threshold model. Numerical simulations of the model in one and two dimensions (with stores arranged on both regular and disordered lattices) illustrate that stochastic calcium release leads to the spontaneous production of calcium sparks that may merge to form saltatory waves. Illustrations of spreading circular waves, spirals and more irregular waves are presented. Furthermore, receptor noise is shown to generate a form of array enhanced coherence resonance whereby all calcium stores release periodically and simultaneously.

Citation

Coombes, S., Hinch, R., & Timofeeva, Y. (2004). Receptors, sparks and waves in a fire-diffuse-fire framework for calcium release

• Journal Article Type: Article
• Publication Date: Feb 1, 2004
• Deposit Date: Feb 17, 2004
• Publicly Available Date: Oct 9, 2007
• Peer Reviewed: Peer Reviewed
• Keywords: calcium sparks, ryanodine receptors, intracellular signalling, fire-diffuse-fire, stochastic transitions, calcium waves
• Public URL: https://nottingham-repository.worktribe.com/output/1021032
• Additional Information: To appear in; Progress in Biophysics and Molecular Biology; Special Issue: Modelling Cellular Function; ; Animations connected with this paper can be found at; http://masc-mac.lboro.ac.uk/~yulia/index.html