Dissecting the Roles of the Autonomic Nervous System and Physical Activity on Circadian Heart Rate Fluctuations in Mice

Barazi, Nour; Polidovitch, Nazari; Debi, Ryan; Yakobov, Simona; Lakin, Robert; Backx, Peter H.

doi:10.3389/fphys.2021.692247

Cited by 11 publications

(26 citation statements)

References 78 publications

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“…We first evaluated the heart rate in vivo, in freely moving conscious WT and Nfix ‐null mice. As expected, we found physiological circadian fluctuations of the heart rate, which is significantly higher during the dark/active than during light/inactive phase 10,20,21 . Recent data clearly demonstrated that these fluctuations persist even after complete pharmacological block of both branches of the autonomic nervous system, and thus rate fluctuations are independent from autonomic modulation 20,21 …”

Section: Discussionsupporting

confidence: 85%

“…As expected, we found physiological circadian fluctuations of the heart rate, which is significantly higher during the dark/active than during light/inactive phase. 10,20,21 Recent data clearly demonstrated that these fluctuations persist even after complete pharmacological block of both branches of the autonomic nervous system, and thus rate fluctuations are independent from autonomic modulation. 20,21 Here we show that Nfix null mice, present a significantly higher heart rate than WT littermates, independently of the light/dark phase of the day.…”

Section: Discussionmentioning

confidence: 99%

“…10,20,21 Recent data clearly demonstrated that these fluctuations persist even after complete pharmacological block of both branches of the autonomic nervous system, and thus rate fluctuations are independent from autonomic modulation. 20,21 Here we show that Nfix null mice, present a significantly higher heart rate than WT littermates, independently of the light/dark phase of the day. Moreover, we found that the higher rate of Nfix-null mice is an intrinsic feature of the SAN, since the tachycardia persists in isolated SAN cardiomyocytes.…”

Section: Discussionmentioning

confidence: 99%

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Lack of the transcription factor Nfix causes tachycardia in mice sinus node and rats neonatal cardiomyocytes

et al. 2023

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AimsNfix is a transcription factor belonging to the Nuclear Factor I (NFI) family comprising four members (Nfia, b, c, x). Nfix plays important roles in the development and function of several organs. In muscle development, Nfix controls the switch from embryonic to fetal myogenesis by promoting fast twitching fibres. In the adult muscle, following injury, lack of Nfix impairs regeneration, inducing higher content of slow‐twitching fibres. Nfix is expressed also in the heart, but its function has been never investigated before. We studied Nfix role in this organ.MethodsUsing Nfix‐null and wild type (WT) mice we analyzed: (1) the expression pattern of Nfix during development by qPCR and (2) the functional alterations caused by its absence, by in vivo telemetry and in vitro patch clamp analysis.Results and ConclusionsNfix expression start in the heart from E12.5. Adult hearts of Nfix‐null mice show a hearts morphology and sarcomeric proteins expression similar to WT. However, Nfix‐null animals show tachycardia that derives form an intrinsic higher beating rate of the sinus node (SAN). Molecular and functional analysis revealed that sinoatrial cells of Nfix‐null mice express a significantly larger L‐type calcium current (Cacna1d + Cacna1c). Interestingly, downregulation of Nfix by sh‐RNA in primary cultures of neonatal rat ventricular cardiomyocytes induced a similar increase in their spontaneous beating rate and in ICaL current. In conclusion, our data provide the first demonstration of a role of Nfix that, increasing the L‐type calcium current, modulates heart rate.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Lack of the transcription factor Nfix causes tachycardia in mice sinus node and rats neonatal cardiomyocytes

et al. 2023

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“…Mouse models of voluntary physical activity show that increased exercise can impact the amplitude of the day/ night rhythm in the HR. Barazi and colleagues 92 compared the day/night rhythms in the HR from anesthetized mice versus telemetry-implanted conscious mice before and after access to running wheels. 92 The anesthetized mice displayed an autonomic nervous system-dependent day/night rhythm in HR.…”

Section: Compendium: Circadian Mechanisms In Cardio/ Cerebrovascular ...mentioning

confidence: 99%

Circadian Regulation of Cardiac Arrhythmias and Electrophysiology

Delisle,

Prabhat,

Burgess

et al. 2024

Circulation Research

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Circadian rhythms in physiology and behavior are ≈24-hour biological cycles regulated by internal biological clocks (ie, circadian clocks) that optimize organismal homeostasis in response to predictable environmental changes. These clocks are present in virtually all cells in the body, including cardiomyocytes. Many decades ago, clinicians and researchers became interested in studying daily patterns of triggers for sudden cardiac death, the incidence of sudden cardiac death, and cardiac arrhythmias. This review highlights historical and contemporary studies examining the role of day/night rhythms in the timing of cardiovascular events, delves into changes in the timing of these events over the last few decades, and discusses cardiovascular disease-specific differences in the timing of cardiovascular events. The current understanding of the environmental, behavioral, and circadian mechanisms that regulate cardiac electrophysiology is examined with a focus on the circadian regulation of cardiac ion channels and ion channel regulatory genes. Understanding the contribution of environmental, behavioral, and circadian rhythms on arrhythmia susceptibility and the incidence of sudden cardiac death will be essential in developing future chronotherapies.

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“…Daily rhythms in physiological behaviour also play an important role in shaping 24 h rhythms in cardiac electrophysiology. Studies show that the amplitude in the 24 h rhythm of the heart rate in mice increased with exercise activity (wheel running) (Barazi et al., 2021). Also, studies that restrict the timing of feeding behaviour of mice to the light cycle (which is inverted to their normal feeding pattern) for several weeks increased the 24 h rhythm amplitudes and means for the RR‐ and QT‐intervals (Schroder et al., 2014).…”

Section: Introductionmentioning

confidence: 99%

The role of the cardiomyocyte circadian clocks in ion channel regulation and cardiac electrophysiology

Schroder

Ono

Johnson

et al. 2022

The Journal of Physiology

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Daily variations in cardiac electrophysiology and the incidence for different types of arrhythmias reflect ≈24 h changes in the environment, behaviour 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 behaviour, have on 24 h 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 h. Several studies now show that 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 h rhythms in heart rate and ventricular repolarization are primarily driven by autonomic signalling. 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 h rhythm in heart rate to abrupt changes in the light cycle. Additional studies show that modifying rhythmic behaviours (including feeding behaviour) can dramatically impact the 24 h rhythms in heart rate and ventricular repolarization. If these mechanisms are conserved, these studies suggest that targeting endogenous circadian mechanisms in the heart, as well as modifying the timing of certain rhythmic behaviours, could emerge as therapeutic strategies to support heart function against perturbations and regulate 24 h rhythms in cardiac electrophysiology.

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Dissecting the Roles of the Autonomic Nervous System and Physical Activity on Circadian Heart Rate Fluctuations in Mice

Cited by 11 publications

References 78 publications

Lack of the transcription factor Nfix causes tachycardia in mice sinus node and rats neonatal cardiomyocytes

Lack of the transcription factor Nfix causes tachycardia in mice sinus node and rats neonatal cardiomyocytes

Circadian Regulation of Cardiac Arrhythmias and Electrophysiology

The role of the cardiomyocyte circadian clocks in ion channel regulation and cardiac electrophysiology

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