Distinct circadian mechanisms govern cardiac rhythms and susceptibility to arrhythmia

Edward A Hayter, Sophie M T Wehrens, Hans P A Van Dongen, Alessandra Stangherlin, Shobhan Gaddameedhi, Elena Crooks, Nichola J Barron, Luigi A Venetucci, John S O' Neill, Timothy M Brown, Debra J Skene, Andrew W Trafford, David A Bechtold

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number2472
JournalNature Communications
Issue number1
Publication statusPublished - 30 Apr 2021


  • ARNTL Transcription Factors/genetics
  • Adult
  • Animals
  • Arrhythmias, Cardiac/genetics
  • Atrioventricular Node/metabolism
  • Autonomic Nervous System/physiology
  • Circadian Clocks/physiology
  • Circadian Rhythm/physiology
  • Electrocardiography
  • Female
  • Gene Expression Regulation/genetics
  • Heart Rate/physiology
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Middle Aged
  • Myocytes, Cardiac/metabolism
  • Sinoatrial Node/metabolism
  • Sleep/physiology


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