Stevenson-Cocks, HJ orcid.org/0000-0003-1044-3545, Colman, MA orcid.org/0000-0003-2817-8508, White, E orcid.org/0000-0002-3954-9792 et al. (1 more author) (2019) Inward Rectifier Current Downregulation Promotes Spontaneous Calcium Release in a Novel Model of Rat Ventricular Electrophysiology. In: Computing in Cardiology. 2018 Computing in Cardiology Conference (CinC), 23-26 Sep 2018, Maastricht, Netherlands. IEEE ISBN 9781728109589
Abstract
Aberrant intracellular calcium handling, as observed in diseases such as heart failure, promotes lethal ventricular arrhythmias and sudden cardiac death. Recent data from our laboratory suggests that reduced expression of the inward rectifier current in failing rat myocytes increases spontaneous calcium release, however existing computational models are unable to reproduce the underlying stochastic calcium cycling dynamics and so we have been unable to use simulation approaches to explore the cause of this pro-arrhythmic behaviour. Here, we develop a novel model of rat ventricular electrophysiology that reproduces normal spatio-temporal calcium dynamics. Simulations implementing a similar reduction in inward rectifier current to that observed experimentally show that spontaneous calcium release is promoted by action potential prolongation and sarcoplasmic reticulum loading in the presence of a depolarised resting membrane potential. Combined, these effects can result in triggered activity. The model therefore provides insight into arrhythmogenic mechanisms in failing ventricular myocytes and can be utilised to further explore pro-arrhythmic behaviour caused by abnormal calcium handling.
Metadata
Item Type: | Proceedings Paper |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018, IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 18 Oct 2019 11:05 |
Last Modified: | 18 Oct 2019 11:05 |
Status: | Published |
Publisher: | IEEE |
Identification Number: | 10.22489/CinC.2018.156 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:152234 |