Distinct circadian mechanisms govern cardiac rhythms and susceptibility to arrhythmia.

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  • Additional Information
    • Source:
      Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
    • Publication Information:
      Original Publication: [London] : Nature Pub. Group
    • Subject Terms:
      Arrhythmias, Cardiac/*physiopathology ; Atrioventricular Node/*physiology ; Circadian Rhythm/*physiology ; Heart Rate/*physiology ; Myocytes, Cardiac/*physiology ; Sinoatrial Node/*physiology; ARNTL Transcription Factors/genetics ; ARNTL Transcription Factors/metabolism ; Adult ; Animals ; Arrhythmias, Cardiac/genetics ; Arrhythmias, Cardiac/metabolism ; Atrioventricular Node/metabolism ; Autonomic Nervous System/physiology ; Circadian Clocks/physiology ; Electrocardiography ; Female ; Gene Expression Regulation/genetics ; Gene Expression Regulation/physiology ; Humans ; Male ; Mice ; Mice, Transgenic ; Middle Aged ; Myocytes, Cardiac/metabolism ; Sinoatrial Node/metabolism ; Sleep/physiology
    • Abstract:
      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.
    • Comments:
      Erratum in: Nat Commun. 2021 Dec 8;12(1):7284. doi: 10.1038/s41467-021-27498-9. (PMID: 34880252)
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    • Grant Information:
      BB/I019405/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; BB/J017744/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; R21 CA227381 United States CA NCI NIH HHS; R00 ES022640 United States ES NIEHS NIH HHS; R01 ES030113 United States ES NIEHS NIH HHS; MC_UP_1201/4 United Kingdom MRC_ Medical Research Council; PG/19/82/34760 United Kingdom BHF_ British Heart Foundation; BB/I018654/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council
    • Accession Number:
      0 (ARNTL Transcription Factors)
      0 (Bmal1 protein, mouse)
    • Publication Date:
      Date Created: 20210501 Date Completed: 20210512 Latest Revision: 20240923
    • Publication Date:
      20240923
    • Accession Number:
      PMC8087694
    • Accession Number:
      10.1038/s41467-021-22788-8
    • Accession Number:
      33931651