![]() A role for the cardiomyocyte clock in cardiac arrhythmogenesis has also been previously implied, but never directly demonstrated 10. ![]() We have recently shown that circadian misalignment driven by altered environmental light/dark cycles or imposed behavioral routine leads to altered cardiac electrophysiology in mice 11 and humans 12. Circadian misalignment can occur when our daily behavioral routine and/or external environment does not match our internal clock timing. Genetic disruption of clock function selectively in cardiomyocytes in mice can slow HR 7, lengthen QT interval 4, and alters ventricular expression of a number of ion channels responsible for electrical conduction in the heart (e.g., Scn5a, Kcnh2) 4, 9, 10. The time-of-day prevalence in many life-threatening cardiac rhythm disorders (e.g., extreme bradycardia, ventricular fibrillation, tachycardia, and sudden cardiac death) is well-documented 1. As a prime example, the SCN contribute to rhythms in HR and heart rate variability (HRV) across the day via the autonomic nervous system 5, 6, yet many aspects of cardiac function including contractility, metabolism, and even recovery from ischemic insult are strongly influenced by the local cardiomyocyte clock 3, 4, 7, 8. Therefore, daily fluctuation in tissue function reflects not only our behavioral state but also the activity of both central and local circadian clock function. Circadian clocks also operate in most cells of the body. The circadian system is orchestrated by a master clock, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, which directs gross rhythms in our physiology (e.g., daily sleep/wake, hormone, and temperature cycles) and keeps us aligned with the external light/dark environment. Importantly, these temporal dynamics are not simply a consequence of the sleep–wake cycle or activity state, but are also heavily influenced by the body’s internal circadian clock 2, 3, 4. ![]() This includes cardiac electrophysiology, where daily rhythms in heart rate (HR) and electrocardiogram (ECG) parameters can be readily observed in humans and laboratory animals 1. Pronounced time-of-day variation exists in most aspects of our cardiovascular physiology.
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