A fire-diffuse-fire framework for the functional organisation of cellular calcium signals
Lead Research Organisation:
University of Nottingham
Department Name: Sch of Mathematical Sciences
Abstract
This work will establish a theoretical underpinning for how cells shape calcium signals in space, time and amplitude using components from a universal signalling toolkit. By considering the combined role of space, noise and heterogeneity in generating the variety of observed calcium signals we will be able to explore the mechanisms which allow a simple ion such as Ca++ to play such a pivotal role in cell biology.The need to make links to experiments forces one to look for cell models that incorporate both the discrete nature of calcium stores and the stochastic nature of calcium release. Work by Coombes on calcium waves in fire-diffuse-fire (FDF) models has focused on the former aspect and has recently been extended to cover the stochastic nature of calcium release. FDF models use a threshold process to mimic the nonlinear properties of Ca++ channels. The stochastic nature of release is incorporated via the introduction of threshold noise. This leads to a model with simple probabilistic update rules for the release of calcium from internal stores. This framework will be extended to include further important aspects of cell physiology known to play an important role in the generation of calcium signals. The development of these mathematical components will be guided by experiments being performed by Bootman and colleagues within the molecular signalling group at the Babraham Institute in Cambridge.
People |
ORCID iD |
Stephen Coombes (Principal Investigator) |
Publications
Bootman MD
(2006)
Calcium signalling during excitation-contraction coupling in mammalian atrial myocytes.
in Journal of cell science
N/a Thul
(2009)
How geometry shapes Calcium signals in atrial myocytes
in Biophysical Journal - in preparation
Thul R
(2008)
A bidomain threshold model of propagating calcium waves.
in Journal of mathematical biology
Thul R
(2012)
Subcellular calcium dynamics in a whole-cell model of an atrial myocyte.
in Proceedings of the National Academy of Sciences of the United States of America
Thul R
(2009)
Sensitisation waves in a bidomain fire-diffuse-fire model of intracellular Ca2+ dynamics
in Physica D: Nonlinear Phenomena
Description | What we perceive as the beating of our heart is actually the co-ordinated action of more than a billion muscle cells. Most of the time, only the muscle cells from the larger heart chambers contract and relax. But when the heart needs to work harder it relies on back-up from the atrial muscle cells deep within the smaller chambers (atria) of the heart. The health of these 'high-performance' atrial cells relies on specific concentrations of cellular calcium. Now, for the first time, scientists at The University of Nottingham have produced a mathematical model of calcium activity within the atrial heart cell which will significantly improve our chances of treating heart disease and stroke. This break-through, which takes scientists into a world of cell activity currently beyond the scope of imaging technology, has just been published in the journal Proceedings of the National Academy of Sciences (PNAS). |
Sectors | Healthcare |
URL | http://www.nottingham.ac.uk/news/pressreleases/2012/february/the-mathematics-of-a-heart-beat-could-save-lives.aspx |
Description | The Babraham Institute |
Organisation | Babraham Institute |
Country | United Kingdom |
Sector | Academic/University |
Start Year | 2006 |