Howlett, L.A. orcid.org/0000-0002-7786-5569, Stevenson‐Cocks, H., Colman, M.A. et al. (2 more authors) (Cover date: July 2023) Ionic current changes underlying action potential repolarization responses to physiological pacing and adrenergic stimulation in adult rat ventricular myocytes. Physiological Reports, 11 (14). e15766. ISSN 2051-817X
Abstract
This study aimed to simulate ventricular responses to elevations in myocyte pacing and adrenergic stimulation using a novel electrophysiological rat model and investigate ion channel responses underlying action potential (AP) modulations. Peak ion currents and AP repolarization to 50% and 90% of full repolarization (APD50-90) were recorded during simulations at 1–10 Hz pacing under control and adrenergic stimulation conditions. Further simulations were performed with incremental ion current block (L-type calcium current, ICa; transient outward current, Ito; slow delayed rectifier potassium current, IKs; rapid delayed rectifier potassium current, IKr; inward rectifier potassium current, IK1) to identify current influence on AP response to exercise. Simulated APD50-90 closely resembled experimental findings. Rate-dependent increases in IKs (6%–101%), IKr (141%–1339%), and ICa (0%–15%) and reductions in Ito (11%–57%) and IK1 (1%–9%) were observed. Meanwhile, adrenergic stimulation triggered moderate increases in all currents (23%–67%) except IK1. Further analyses suggest AP plateau is most sensitive to modulations in Ito and ICa while late repolarization is most sensitive to IK1, ICa, and IKs, with alterations in IKs predominantly stimulating the greatest magnitude of influence on late repolarization (35%–846% APD90 prolongation). The modified Leeds rat model (mLR) is capable of accurately modeling APs during physiological stress. This study highlights the importance of ICa, Ito, IK1, and IKs in controlling electrophysiological responses to exercise. This work will benefit the study of cardiac dysfunction, arrythmia, and disease, though future physiologically relevant experimental studies and model development are required.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 The Authors. This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | action potential, computational modeling, electrophysiology, exercise, ion currents, repolarization |
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) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biology (Leeds) |
Funding Information: | Funder Grant number British Heart Foundation PG/16/74/32374 |
Depositing User: | Symplectic Publications |
Date Deposited: | 28 Jul 2023 08:19 |
Last Modified: | 11 Sep 2024 16:21 |
Status: | Published |
Publisher: | Wiley Open Access |
Identification Number: | 10.14814/phy2.15766 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:201942 |