TY - JOUR
T1 - Timing of food intake in mice unmasks a role for the cardiomyocyte circadian clock mechanism in limiting QT-interval prolongation
AU - Schroder, Elizabeth A.
AU - Burgess, Don E.
AU - Johnson, Sidney R.
AU - Ono, Makoto
AU - Seward, Tanya
AU - Elayi, Claude S.
AU - Esser, Karyn A.
AU - Delisle, Brian P.
N1 - Publisher Copyright:
© 2021 Taylor & Francis Group, LLC.
PY - 2022
Y1 - 2022
N2 - Cardiac electrophysiological studies demonstrate that restricting the feeding of mice to the light cycle (time restricted feeding or TRF) causes a pronounced change in heart rate and ventricular repolarization as measured by the RR- and QT-interval, respectively. TRF slows heart rate and shifts the peak (acrophase) of the day/night rhythms in the RR- and QT-intervals from the light to the dark cycle. This study tested the hypothesis that these changes in cardiac electrophysiology are driven by the cardiomyocyte circadian clock mechanism. We determined the impact that TRF had on RR- and QT-intervals in control mice or mice that had the cardiomyocyte circadian clock mechanism disrupted by inducing the deletion of Bmal1 in adult cardiomyocytes (iCSΔBmal1 −/− mice). In control and iCSΔBmal1 −/− mice, TRF increased the RR-intervals measured during the dark cycle and shifted the acrophase of the day/night rhythm in the RR-interval from the light to the dark cycle. Compared to control mice, TRF caused a larger prolongation of the QT-interval measured from iCSΔBmal1 −/− mice during the dark cycle. The larger QT-interval prolongation in the iCSΔBmal1 −/− mice caused an increased mean and amplitude in the day/night rhythm of the QT-interval. There was not a difference in the TRF-induced shift in the day/night rhythm of the QT-interval measured from control or iCSΔBmal1 −/− mice. We conclude that the cardiomyocyte circadian clock does not drive the changes in heart rate or ventricular repolarization with TRF. However, TRF unmasks an important role for the cardiomyocyte circadian clock to prevent excessive QT-interval prolongation, especially at slow heart rates.
AB - Cardiac electrophysiological studies demonstrate that restricting the feeding of mice to the light cycle (time restricted feeding or TRF) causes a pronounced change in heart rate and ventricular repolarization as measured by the RR- and QT-interval, respectively. TRF slows heart rate and shifts the peak (acrophase) of the day/night rhythms in the RR- and QT-intervals from the light to the dark cycle. This study tested the hypothesis that these changes in cardiac electrophysiology are driven by the cardiomyocyte circadian clock mechanism. We determined the impact that TRF had on RR- and QT-intervals in control mice or mice that had the cardiomyocyte circadian clock mechanism disrupted by inducing the deletion of Bmal1 in adult cardiomyocytes (iCSΔBmal1 −/− mice). In control and iCSΔBmal1 −/− mice, TRF increased the RR-intervals measured during the dark cycle and shifted the acrophase of the day/night rhythm in the RR-interval from the light to the dark cycle. Compared to control mice, TRF caused a larger prolongation of the QT-interval measured from iCSΔBmal1 −/− mice during the dark cycle. The larger QT-interval prolongation in the iCSΔBmal1 −/− mice caused an increased mean and amplitude in the day/night rhythm of the QT-interval. There was not a difference in the TRF-induced shift in the day/night rhythm of the QT-interval measured from control or iCSΔBmal1 −/− mice. We conclude that the cardiomyocyte circadian clock does not drive the changes in heart rate or ventricular repolarization with TRF. However, TRF unmasks an important role for the cardiomyocyte circadian clock to prevent excessive QT-interval prolongation, especially at slow heart rates.
KW - Bmal1
KW - QT-interval
KW - Restricted feeding
KW - cardiac electrophysiology
KW - circadian clock
KW - circadian rhythms
KW - heart rate
KW - ventricular repolarization
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U2 - 10.1080/07420528.2021.2011307
DO - 10.1080/07420528.2021.2011307
M3 - Article
C2 - 34875962
AN - SCOPUS:85121389803
SN - 0742-0528
VL - 39
SP - 525
EP - 534
JO - Chronobiology International
JF - Chronobiology International
IS - 4
ER -