期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-22788-8
关键词
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资金
- UK Biotechnology and Biological Sciences Research Council (BBSRC) [BB/J017744/1, BB/I018654/1]
- AstraZeneca Blue Skies Initiative
- Medical Research Council [MC_UP_1201/4]
- EU Marie Curie Research Training Network grant [CT-2004-512362]
- project EUCLOCK [018741]
- Stockgrand Ltd (University of Surrey)
- College of Pharmacy and Pharmaceutical Sciences at Washington State University
- Congressionally Directed Medical Research Program
- U.S. Army Medical Research and Development Command [W81XWH-16-1-0319, W81XWH-18-1-0100, W81XWH-20-1-0442]
- National Institutes of Health [R01ES030113, R21CA227381]
- BBSRC [BB/I019405/1]
- EU [278397]
- BBSRC [BB/I018654/1, BB/J017744/1] Funding Source: UKRI
The electrical activity of the heart is regulated by circadian clocks in the brain and heart, leading to time-dependent susceptibility to arrhythmias. Different inputs from the autonomic nervous system and cardiomyocyte clock affect the SA and AV nodes, making the cardiac conduction system sensitive to abrupt changes in behavior and sleep-wake timing.
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. Cardiac function fluctuates greatly across the day and night, but this is not simply a consequence of our changing behaviour. The authors highlight the role of the body's circadian clock in regulating the heart electrical activity, including a time-of-day dependent susceptibility to cardiac arrhythmias.
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