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Daily variations in cardiac electrophysiology and the incidence for different types of arrhythmias reflect ≈24-hour changes in the environment, behavior, and internal circadian rhythms. This article focuses on studies that use animal models to separate the impact that circadian rhythms, as well as changes in the environment and behavior, have on 24-hour rhythms in heart rate and ventricular repolarization. Circadian rhythms are initiated at the cellular level by circadian clocks, transcription-translation feedback loops that cycle with a periodicity of 24-hours. Several studies now show the circadian clock in cardiomyocytes regulates the expression of cardiac ion channels by multiple mechanisms; underlies time-of-day changes in sinoatrial node excitability/intrinsic heart rate; and limits the duration of the ventricular action potential waveform. However, the 24-hour rhythms in heart rate and ventricular repolarization are primarily driven by autonomic signaling. A functional role for the cardiomyocyte circadian clock appears to buffer the heart against perturbations. For example, the cardiomyocyte circadian clock limits QT-interval prolongation (especially at slower heart rates), and it may facilitate the realignment of the 24-hour rhythm in heart rate to abrupt changes in the light cycle. Additional studies show modifying rhythmic behaviors (including feeding behavior) can dramatically impact the 24-hour rhythms in heart rate and ventricular repolarization. If these mechanisms are conserved, these studies suggest targeting endogenous circadian mechanisms in the heart, as well as modifying the timing of certain rhythmic behaviors, could emerge as therapeutic strategies to support heart function against perturbations and regulate 24-hour rhythms in cardiac electrophysiology. |
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