Dynamics of Calcium release and wave propagation in single cells
The existence of spatial and temporal signalling by calcium is one of the most significant findings of the last decade in the field of intracellular signalling. Calcium is stored intracellularly in the endoplasmic or sarcoplasmic reticulum at 2-3 orders of magnitude greater than its concentration in the cytosol and is released by a nonlinear feedback process referred to as calcium-induced calcium release (CICR). This mechanism for generating oscillations (or puffs) in the density of cytosolic free calcium is believed to underly the waves that propagate as intra and intercellular waves over distance as large as 1mm.
I am interested in both the numerical solution of biophysical models (such as the de-Young/Keizer model) using techniques from dynamical systems theory and the exact solution of fire-diffues-fire type models. The analysis of wave initiation and propagation in models with spatial inhomogeneities and nonlinear transport mechanisms is relevant to the understanding of recent experimental work by Martin Bootman and colleagues.
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Relevant publications:
| S Coombes 2001 The effect of ion pumps on the speed of travelling waves in the fire-diffuse-fire model of Ca2+ release, Bulletin of Mathematical Biology, Vol 63, 1-20 |
| Y Timofeeva and S Coombes 2003 Wave bifurcation and propagation failure in a model of Calcium release, Journal of Mathematical Biology, Vol 47, 249-269 |
| S Coombes and Y Timofeeva 2003 Sparks and waves in a stochastic fire-diffuse-fire model of Calcium release, Physical Review E, Vol 68, 021915 |
| S Coombes, R Hinch and Y Timofeeva 2004 Receptors, sparks and waves in a fire-diffuse-fire framework for calcium release, Progress in Biophysics and Molecular Biology, Vol 85, 197-216 |
| M D Bootman, D R Higazi, S Coombes and H L Roderick 2006 Calcium signalling during excitation-contraction coupling in mammalian atrial myocytes, Journal of Cell Science, Vol 119, 3915-3925 |
| R Thul, T C Bellamy, H L Roderick, M D Bootman and S Coombes 2008 Calcium Oscillations, Cellular Oscillatory Mechanisms (Ed. Miguel Maroto and Nick Monk), Springer, Advances in Experimental Medicine and Biology |
| R Thul, G D Smith and S Coombes 2008 A bidomain threshold model of propagating calcium waves, Journal of Mathematical Biology, Vol 56, 435-463 |
| R Thul, S Coombes and G D Smith 2009 Sensitisation of waves in a bidomain fire-diffuse-fire model of intracellular Ca2+ dynamics, Physica D, Vol 238, 2142-2152 |
| M D Bootman, R Thul, S Coombes and H L Roderick 2011 Atrial cardiomyocyte calcium signalling, Biochimica et Biophysica Acta, Vol 1813, 922-934 |
| R Thul, S Coombes, H L Roderick and M D Bootman 2012 Subcellular calcium dynamics in a whole cell model of an atrial myocyte, Proceedings of the National Academy of Sciences, Vol 109, 2150-2155 |
| R Thul, S Coombes and M D Bootman 2012 Persistence of pro-arrhythmic spatio-temporal calcium patterns in atrial myocytes: a computational study of ping waves, Frontiers in Computational Physiology and Medicine, Vol 3, 279 |
| R Thul, K Rietdorf, M D Bootman and S Coombes 2015 Unifying principles of calcium wave propagation - insights from a three-dimensional model for atrial myocytes, Biochimica et Biophysica Acta Molecular Cell Research, Vol 1853(9), 2131–2143 |