Al-Owais, MM, Steele, DS, Holden, AV et al. (1 more author) (2021) Deterministic and Stochastic Cellular Mechanisms Contributing to Carbon Monoxide Induced Ventricular Arrhythmias. Frontiers in Pharmacology, 12. 651050. ISSN 1663-9812
Abstract
Chronic exposure to low levels of Carbon Monoxide is associated with an increased risk of cardiac arrhythmia. Microelectrode recordings from rat and guinea pig single isolated ventricular myocytes exposed to CO releasing molecule CORM-2 and excited at 0.2/s show repolarisation changes that develop over hundreds of seconds: action potential prolongation by delayed repolarisation, EADs, multiple EADs and oscillations around the plateau, leading to irreversible repolarisation failure. The measured direct effects of CO on currents in these cells, and ion channels expressed in mammalian systems showed an increase in prolonged late Na+, and a decrease in the maximal T- and L-type Ca++. peak and late Na+, ultra-rapid delayed, delayed rectifier, and the inward rectifier K+ currents. Incorporation of these CO induced changes in maximal currents in ventricular cell models; (Gattoni et al., J. Physiol., 2016, 594, 4193–4224) (rat) and (Luo and Rudy, Circ. Res., 1994, 74, 1071–1096) (guinea-pig) and human endo-, mid-myo- and epi-cardial (O’Hara et al., PLoS Comput. Biol., 2011, 7, e1002061) models, by changes in maximal ionic conductance reproduces these repolarisation abnormalities. Simulations of cell populations with Gaussian distributions of maximal conductance parameters predict a CO induced increase in APD and its variability. Incorporation of these predicted CO induced conductance changes in human ventricular cell electrophysiology into ventricular tissue and wall models give changes in indices for the probability of the initiation of re-entrant arrhythmia.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 Al-Owais, Steele, Holden and Benson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
Keywords: | carbon monoxide, ion channels, arrhythmias, modeling, potassium channels, action potential duration |
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: | 29 Apr 2021 15:21 |
Last Modified: | 25 Jun 2023 22:38 |
Status: | Published |
Publisher: | Frontiers Media |
Identification Number: | 10.3389/fphar.2021.651050 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:173514 |