Distinct circadian mechanisms govern cardiac rhythms and susceptibility to arrhythmia

Edward Hayter; Sophie Wehrens; Hans P A Van Dongen; Alessandra Stangherlin; Shobhan Gaddameedhi; Elena Crooks; Nichola Barron; Luigi Venetucci; John S. O’Neill; Timothy M Brown; DEBRA JEAN SKENE; Andrew Trafford; David Bechtold

doi:10.1038/s41467-021-22788-8

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Distinct circadian mechanisms govern cardiac rhythms and susceptibility to arrhythmia

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Distinct circadian mechanisms govern cardiac rhythms and susceptibility to arrhythmia

Edward Hayter, Sophie Wehrens, Hans P A Van Dongen, Alessandra Stangherlin, Shobhan Gaddameedhi, Elena Crooks, Nichola Barron, Luigi Venetucci, John S. O’Neill, Timothy M Brown, …

Nature communications

30/04/2021

DOI: https://doi.org/10.1038/s41467-021-22788-8

Abstract

Arrhythmias

Circadian regulation

Sleep deprivation

Electrical activity in the heart exhibits 24-hour rhythmicity, and potentially fatal arrhythmias are more likely to occur at specific times of day. Here, we demonstrate that circadian clocks within the brain and heart set daily rhythms in sinoatrial (SA) and atrioventricular (AV) node activity, and impose a time-of–day dependent susceptibility to ventricular arrhythmia. Critically, the balance of circadian inputs from the autonomic nervous system and cardiomyocyte clock to the SA and AV nodes differ, and this renders the cardiac conduction system sensitive to decoupling during abrupt shifts in behavioural routine and sleep-wake timing. Our findings reveal a functional segregation of circadian control across the heart’s conduction system and inherent susceptibility to arrhythmia.

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Title: Distinct circadian mechanisms govern cardiac rhythms and susceptibility to arrhythmia
Creators: Edward Hayter
Sophie Wehrens
Hans P A Van Dongen
Alessandra Stangherlin
Shobhan Gaddameedhi
Elena Crooks
Nichola Barron
Luigi Venetucci
John S. O’Neill
Timothy M Brown
DEBRA JEAN SKENE - University of Surrey, School of Biosciences
Andrew Trafford
David Bechtold
Publication Details: Nature communications
Publisher: Nature Research
Date published: 30/04/2021
Date accepted: 26/03/2021
Grants: Biological resonance: matching internal timing to environmental fluctuations, BB/J017744/1, Biotechnology and Biological Sciences Research Council (United Kingdom, Swindon) - BBSRC
Circadian contol of metabolism: implications for health and disease, BB/I018654/1, Biotechnology and Biological Sciences Research Council (United Kingdom, Swindon) - BBSRC
Grant note: We would like to thank the Biological Services Units at the University of Manchester and Laboratory of Molecular Biology for their excellent support of the animal work. We also thank our funders for their generous support: UK Biotechnology and Biological Sciences Research Council (BBSRC) grants to D.A.B. (BB/J017744/1; BB/I018654/1); AstraZeneca Blue Skies Initiative and the Medical Research Council (MC_UP_1201/4) to J.S.O.; Human study one was supported by an EU Marie Curie Research Training Network grant (CT-2004-512362) to D.J.S., 6th Framework project EUCLOCK (018741) to D.J.S. and Stockgrand Ltd (University of Surrey) to S.M.T.W. and D.J.S. Human study two was supported by start-up funds from the College of Pharmacy and Pharmaceutical Sciences at Washington State University to S.G. and by Congressionally Directed Medical Research Program and U.S. Army Medical Research and Development Command awards W81XWH-16-1-0319, W81XWH-18-1-0100 and W81XWH-20-1-0442 to H.P.A.V.D.; National Institutes of Health Grants R01ES030113 and R21CA227381 to S.G.; BBSRC Grant BB/I019405/1 to D.J.S.; and EU FP7-HEALTH-2011 EuRhythDia Grant 278397 to D.J.S.
Identifiers: 99550923302346
Copyright: Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Academic Unit: School of Biosciences
Resource Type: Journal article
SDG (Scopus 2023): SDG 3

Distinct circadian mechanisms govern cardiac rhythms and susceptibility to arrhythmia

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