4.6 Article

Non-canonical role of the sympathetic nervous system in the day-night rhythm in heart rate

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ROYAL SOC
DOI: 10.1098/rstb.2022.0179

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heart rate; sinus node; pacemaking; circadian rhythm; sympathetic nervous system

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Although the day-night rhythm in resting heart rate has traditionally been attributed to the parasympathetic nervous system, recent research shows that there is a circadian clock in the cardiac pacemaker and the rhythm in heart rate involves transcriptional remodelling of pacemaker ion channels. This study investigates the role of the sympathetic nervous system in this rhythm and finds that it directly affects pacemaker ion channel transcription. Understanding the day-night rhythm in pacemaking improves our knowledge of bradyarrhythmias during sleep.
Although, for many decades, the day-night rhythm in resting heart rate has been attributed to the parasympathetic branch of the autonomic nervous system (high vagal tone during sleep), recently we have shown that there is a circadian clock in the cardiac pacemaker, the sinus node, and the day-night rhythm in heart rate involves an intrinsic rhythmic transcriptional remodelling of pacemaker ion channels, particularly Hcn4. We have now investigated the role of the sympathetic branch of the autonomic nervous system in this and shown it to have a non-canonical role. In mice, sustained long-term block of cardiac beta-adrenergic receptors by propranolol administered in the drinking water abolished the day-night rhythm in pacemaking in the isolated sinus node. Concomitant with this, there was a loss of the normal day-night rhythm in many pacemaker ion channel transcripts. However, there was little or no change in the local circadian clock, indicating that the well-known day-night rhythm in sympathetic nerve activity is directly involved in pacemaker ion channel transcription. The day-night rhythm in pacemaking helps explain the occurrence of clinically significant bradyarrhythmias during sleep, and this study improves our understanding of this pathology.This article is part of the theme issue 'The heartbeat: its molecular basis and physiological mechanisms'.

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