Abstract
Circadian rhythms are generated by cell autonomous circadian clocks that perform a ubiquitous cellular time-keeping function and cell type-specific functions important for normal physiology. Studies show inducing the deletion of the core circadian clock transcription factor Bmal1 in adult mouse cardiomyocytes disrupts cardiac circadian clock function, cardiac ion channel expression, slows heart rate, and prolongs the QT-interval at slow heart rates. This study determined how inducing the deletion of Bmal1 in adult cardiomyocytes impacted the in vivo electrophysiological phenotype of a knock-in mouse model for the arrhythmogenic long QT syndrome (Scn5a+/ΔKPQ). Electrocardiographic telemetry showed inducing the deletion of Bmal1 in the cardiomyocytes of mice with or without the ΔKPQ-Scn5a mutation increased the QT-interval at RR-intervals that were ≥130 ms. Inducing the deletion of Bmal1 in the cardiomyocytes of mice with or without the ΔKPQ-Scn5a mutation also increased the day/night rhythm-adjusted mean in the RR-interval, but it did not change the period, phase or amplitude. Compared to mice without the ΔKPQ-Scn5a mutation, mice with the ΔKPQ-Scn5a mutation had reduced heart rate variability (HRV) during the peak of the day/night rhythm in the RR-interval. Inducing the deletion of Bmal1 in cardiomyocytes did not affect HRV in mice without the ΔKPQ-Scn5a mutation, but it did increase HRV in mice with the ΔKPQ-Scn5a mutation. The data demonstrate that deleting Bmal1 in cardiomyocytes exacerbates QT- and RR-interval prolongation in mice with the ΔKPQ-Scn5a mutation.
Document Type
Article
Publication Date
6-24-2021
Digital Object Identifier (DOI)
https://doi.org/10.3389/fphys.2021.681011
Funding Information
This work was supported by National Heart Lung and Blood Institute grants R01HL153042, R01HL141343, and the American Heart Association grant 16GRNT30800003.
Related Content
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
Repository Citation
Schroder, Elizabeth A.; Wayland, Jennifer L.; Samuels, Kaitlyn M.; Shah, Syed F.; Burgess, Don E.; Seward, Tanya S.; Elayi, Claude S.; Esser, Karyn A.; and Delisle, Brian P., "Cardiomyocyte Deletion of Bmal1 Exacerbates QT- and RR-Interval Prolongation in Scn5a+/ΔKPQ Mice" (2021). Physiology Faculty Publications. 173.
https://uknowledge.uky.edu/physiology_facpub/173
Notes/Citation Information
Published in Frontiers in Physiology, v. 12, article 681011.
© 2021 Schroder, Wayland, Samuels, Shah, Burgess, Seward, Elayi, Esser and Delisle
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