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ToR-ORd-dynCl: an update of the ToR-ORd model of human ventricular cardiomyocyte with dynamic intracellular chloride

View ORCID ProfileJakub Tomek, View ORCID ProfileAlfonso Bueno-Orovio, View ORCID ProfileBlanca Rodriguez
doi: https://doi.org/10.1101/2020.06.01.127043
Jakub Tomek
1Department of Anatomy, Physiology, and Genetics, University of Oxford
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  • For correspondence: [email protected]
Alfonso Bueno-Orovio
2Department of Computer Science, University of Oxford
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Blanca Rodriguez
2Department of Computer Science, University of Oxford
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Abstract

Recently, our group published a new model of human ventricular cardiomyocyte named ToR-ORd (Tomek et al., 2019). Its development, calibration, and validation, were performed using a broad range of human experimental data and brought general insights into modelling of ionic channels. Model calibration ensured the reproduction of key physiological cellular features, with independent multiscale validation demonstrating a correct response to channel blocking drugs and pathophysiological remodelling.

However, for very long simulations (several hours rather than minutes), the ToR-ORd simulations display a drift in its behaviour, caused by modelling chloride concentrations as constant values. This may be a limitation for simulations considering extremely long protocols, or for studies on model stability. To remedy this, we present here an updated version, termed ToR-ORd-dynCl, with dynamic representation of intracellular chloride. This model behaves very similarly to the original ToR-ORd, but with stable properties over long simulations and only a small increase in model complexity.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted June 01, 2020.
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ToR-ORd-dynCl: an update of the ToR-ORd model of human ventricular cardiomyocyte with dynamic intracellular chloride
Jakub Tomek, Alfonso Bueno-Orovio, Blanca Rodriguez
bioRxiv 2020.06.01.127043; doi: https://doi.org/10.1101/2020.06.01.127043
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ToR-ORd-dynCl: an update of the ToR-ORd model of human ventricular cardiomyocyte with dynamic intracellular chloride
Jakub Tomek, Alfonso Bueno-Orovio, Blanca Rodriguez
bioRxiv 2020.06.01.127043; doi: https://doi.org/10.1101/2020.06.01.127043

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