The role of the cardiomyocyte circadian clocks in ion channel regulation and cardiac electrophysiology.
The role of the cardiomyocyte circadian clocks in ion channel regulation and cardiac electrophysiology.
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DOI：
10.1113/jp282402
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发表时间：
2022-05
影响因子：
5.5
通讯作者：
Delisle, Brian P.
中科院分区：
文献类型：
--
作者：
Schroder, Elizabeth A.;Ono, Makoto;Johnson, Sidney R.;Rozmus, Ezekiel R.;Burgess, Don E.;Esser, Karyn A.;Delisle, Brian P.
关键词：
心脏电生理的每日变化和不同类型心律失常的发生率反映了环境、行为和内部昼夜节律的24小时变化。本文重点介绍了使用动物模型来分离昼夜节律以及环境和行为变化对心率和心室复极24小时节律的影响的研究。昼夜节律在细胞水平上由昼夜节律钟启动，昼夜节律钟是以24小时为周期循环的转录-翻译反馈回路。一些研究表明，心肌细胞中的生物钟通过多种机制调节心脏离子通道的表达;是窦房结兴奋性/固有心率的时间变化的基础;并限制心室动作电位波形的持续时间。然而，心率和心室复极的24小时节律主要由自主信号驱动。心肌细胞生物钟的功能作用似乎是缓冲心脏对扰动。例如，心肌细胞生物钟限制QT间期延长（特别是在心率较慢的情况下），并且它可能促进心率中的24小时节律与光周期中的突然变化的重新对齐。其他研究表明，改变节律行为（包括进食行为）可以显著影响心率和心室复极的24小时节律。如果这些机制是保守的，这些研究表明，靶向心脏中的内源性昼夜节律机制，以及修改某些节律行为的时间，可能会成为支持心脏功能对抗扰动和调节心脏电生理学24小时节律的治疗策略。
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.