Ab34-3

Tong, Mengmeng; Watanabe, Eiichi; Yamamoto, Naoki; Nagahata-Ishiguro, Misao; Maemura, Koji; Takeda, Norihiko; Nagai, Ryoji; Kodama, Itsuo

doi:10.1016/j.hrthm.2006.02.221

Cited by 2 publications

(4 citation statements)

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“…Similar results have been obtained by others: rhythmicity in cardiac clock gene expression is maintained in Dbh −/− mice, which are deficient in dopamine β-hydroxylase, an enzyme required for catecholamine synthesis [30]. Furthermore, in studies of sustained blockade of the sympathetic nervous system in mice and rats, rhythmicity in atrial and ventricular clock transcripts continued [20,31]. Our working hypothesis is that the day-night rhythm in sympathetic activity directly causes (or contributes to-see below) a day-night rhythm in ion channel transcription; this explains why the rhythms in ion channel transcription are disrupted with sustained β-adrenergic receptor blockade.…”

Section: Discussionsupporting

confidence: 86%

“…Following sustained β-adrenergic receptor blockade, we also observed alterations in the rhythmic expression of several transcripts in the left ventricle that are known to underpin excitation-contraction coupling, including Ryr2, Slc8a1 and Pln (ryanodine receptor, Na + -Ca 2+ exchanger and phospholamban; electronic supplementary material, figure S6a-c). Interestingly, in the left ventricle, there was a marked change in Kcnd2 (K v 4.2; electronic supplementary material, figure S6f ), which has previously been shown to be altered in the ventricle following sustained double autonomic blockade [20], and in Kcnh2 (ERG; electronic supplementary material, figure S6g), which is known to be regulated by the local cardiac circadian clock [26].…”

Section: (A) Effect Of Sustained β-Adrenergic Receptor Blockade In Vivomentioning

confidence: 95%

“…However, questions remain. In contrast with shortterm pharmacological autonomic blockade, long-term pharmacological sympathetic nervous system blockade reduces or abolishes the day-night rhythm in the resting heart rate [1,[19][20][21]. This raises the possibility of a non-canonical role (i.e.…”

Section: Introductionmentioning

confidence: 99%

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

Anderson

Forte

Wei

et al. 2023

Phil. Trans. R. Soc. B

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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 β-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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Section: Discussionsupporting

confidence: 86%

Section: (A) Effect Of Sustained β-Adrenergic Receptor Blockade In Vivomentioning

confidence: 95%

See 1 more Smart Citation

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

Anderson

Forte

Wei

et al. 2023

Phil. Trans. R. Soc. B

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“…Cardiac repolarization results from a concerted balance of depolarizing inward currents (mainly Ca 2+ currents) and repolarizing outward currents (mainly K + currents) in ventricular cells. Strong evidences for a circadian pattern of cardiac K + channels have been provided both in rodent and human heart 19,23,24,[27][28][29][30] . Only a couple of controversial studies have assessed the circadian variation the ventricular L-type Ca 2+ channel (LTCC) [31][32][33][34][35] , primarily composed of the Ca V 1.2 pore-forming subunit (encoded by CACNA1C), Ca V β2 and Ca V α2δ1 auxiliary subunits (encoded by CACNB2 and CACNA2D1, respectively) 36 .…”

Section: Introductionmentioning

confidence: 99%

Circadian regulation of Ca_V1.2 expression by RORα in the mouse heart

Personnic,

Gerard,

Poilbout

et al. 2024

Preprint

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Background. In addition to show autonomous beating rhythmicity, the physiological functions of the heart present daily periodic oscillations. Notably the ventricular repolarization itself varies throughout the circadian cycle which was mainly related to the periodic expression of K+ channels. However, the involvement of the L-type Ca2+ channel (CaV) 1.2 encoded by Cacna1c gene) in these circadian variations remains elusive. Methods. We used a transgenic mouse model (PCa-luc) that expresses the luciferase reporter under the control of the cardiac Cacna1c promoter and analyzed promoter activity by bioluminescent imaging, qPCR, immunoblot, Chromatin immunoprecipitation assay (ChIP) and CaV1.2 activity. Results. Under normal 12:12h light-dark cycle, we observed in vivo a biphasic diurnal variation of promoter activities peaking at 9 and 19.5 Zeitgeber time (ZT). This was associated with a periodicity of Cacna1c mRNA levels preceding 24-h oscillations of CaV1.2 protein levels in ventricle (with a 1.5 h phase shift) but not in atrial heart tissues. The periodicity of promoter activities and CaV1.2 proteins, which correlated with biphasic oscillations of L-type Ca2+ current conductance, persisted in isolated ventricular cardiomyocytes from PCa-Luc mice over the course of the 24-h cycle, suggesting an endogenous cardiac circadian regulation. Comparison of 24-h temporal patterns of clock gene expressions in ventricles and atrial tissues of the same mice revealed conserved circadian oscillations of the core clock genes except for the retinoid-related orphan receptor alpha gene (RORalpha), which remained constant throughout the course of a day in atrial tissues. In vitro we found that RORalpha is recruited to two specific regions on the Cacna1c promoter and that incubation with specific RORalpha inhibitor disrupted 24-h oscillations of ventricular promoter activities and CaV1.2 protein levels. Similar results were observed for pore forming subunits of the K+ transient outward currents, KV4.2 and KV4.3. Conclusions. These findings raise the possibility that the RORalpha-dependent rhythmic regulation of cardiac CaV1.2 and KV4.2/4.3 throughout the daily cycle may play an important role in physiopathology of heart function.

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Ab34-3

Cited by 2 publications

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

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

Circadian regulation of Ca_V1.2 expression by RORα in the mouse heart

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Ab34-3

Cited by 2 publications

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

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

Circadian regulation of CaV1.2 expression by RORα in the mouse heart

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Circadian regulation of Ca_V1.2 expression by RORα in the mouse heart