Modelling modal gating of ion channels with hierarchical Markov models
2016 | journal article. A publication with affiliation to the University of Göttingen.
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Modelling modal gating of ion channels with hierarchical Markov models
Siekmann, I.; Fackrell, M.; Crampin, E. J. & Taylor, P. (2016)
PROCEEDINGS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES, 472(2192) art. 20160122. DOI: https://doi.org/10.1098/rspa.2016.0122
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- Authors
- Siekmann, Ivo; Fackrell, Mark; Crampin, Edmund J.; Taylor, Peter
- Abstract
- Many ion channels spontaneously switch between different levels of activity. Although this behaviour known as modal gating has been observed for a long time it is currently not well understood. Despite the fact that appropriately representing activity changes is essential for accurately capturing time course data from ion channels, systematic approaches for modelling modal gating are currently not available. In this paper, we develop a modular approach for building such a model in an iterative process. First, stochastic switching between modes and stochastic opening and closing within modes are represented in separate aggregated Markov models. Second, the continuous-time hierarchical Markov model, a new modelling framework proposed here, then enables us to combine these components so that in the integrated model both mode switching as well as the kinetics within modes are appropriately represented. A mathematical analysis reveals that the behaviour of the hierarchical Markov model naturally depends on the properties of its components. We also demonstrate how a hierarchical Markov model can be parametrized using experimental data and show that it provides a better representation than a previous model of the same dataset. Because evidence
- Issue Date
- 2016
- Status
- published
- Publisher
- Royal Soc
- Journal
- PROCEEDINGS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES
- ISSN
- 1471-2946; 1364-5021