ArticleAmerican journal of physiology. Cell physiology2013
The cardiomyocyte molecular clock, regulation of Scn5a, and arrhythmia susceptibility.
Article in American journal of physiology. Cell physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
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Who cites it
100 citing papers in PubMed, 142 citations in OpenAlex.
- BMAL1 in cardiovascular diseases: Molecular mechanisms, circadian regulation and translational perspectives (Review).Molecular medicine reports · 2026Review
- Timing of food intake impacts cardiovascular and neuroendocrine physiology and risk of disease.Cardiovascular research · 2026Review
- Eating jetlag based on meal timing discrepancies and risk of cardiovascular disease using the prospective cohort NutriNet-Santé.Communications medicine · 2026Article
- Circadian regulation of cardiovascular function: from physiology to clinical implications.Genome medicine · 2026Review
- BMAL1 mediates sex-specific circadian regulation of cardiac ion channels and temporal arrhythmia vulnerability.Heart rhythm · 2026Article
- ANGPTL2 and CP define complementary circadian-associated signals in atrial fibrillation: integrative transcriptomics and external validation.Frontiers in cell and developmental biology · 2026Article
- Neurobiology of the circadian clock and its role in cardiovascular disease: Mechanisms, biomarkers, and chronotherapy.Neurobiology of sleep and circadian rhythms · 2025Review
- The clinical impact of chronopharmacology on current medicine.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Parallel and convergent evolution in genes underlying seasonal migration.Evolution letters · 2025Article
- Heart Failure and Arrhythmias: Circadian and Epigenetic Interplay in Myocardial Electrophysiology.International journal of molecular sciences · 2025Review
- Circadian influences on sudden cardiac death and cardiac electrophysiology.Journal of molecular and cellular cardiology · 2025Review
- BMAL1 is a Critical Regulator of Sex-Specific Gene Expression in the Heart.Function (Oxford, England) · 2025Article
- The Core Circadian Clock Factor, Bmal1, Transduces Sex-specific Differences in Both Rhythmic and Nonrhythmic Gene Expression in the Mouse Heart.Function (Oxford, England) · 2025Article
- Circadian biology of cardiac aging.Journal of molecular and cellular cardiology · 2025Review
- Social jetlag alters markers of exercise-induced mitochondrial adaptations in the heart.Npj biological timing and sleep · 2025Article
- Dim light at night unmasks sex-specific differences in circadian and autonomic regulation of cardiovascular physiology.Communications biology · 2024Article
- Circadian rhythms in cardiovascular (dys)function: approaches for future therapeutics.NPJ cardiovascular health · 2024Review
- Chronobiotic and cytoprotective activity of melatonin in the cardiovascular system. Doses matter.Npj biological timing and sleep · 2024Review
- Feeding behavior modifies the circadian variation in RR and QT intervals by distinct mechanisms in mice.American journal of physiology. Regulatory, integrative and comparative physiology · 2024Article
- Cardiac GR Mediates the Diurnal Rhythm in Ventricular Arrhythmia Susceptibility.Circulation research · 2024Article
40 more citing papers are in PubMed but not listed here.
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10 authors at 2 institutions in 1 country.
Funding
Abstract
The molecular clock mechanism underlies circadian rhythms and is defined by a transcription-translation feedback loop. Bmal1 encodes a core molecular clock transcription factor. Germline Bmal1 knockout mice show a loss of circadian variation in heart rate and blood pressure, and they develop dilated cardiomyopathy. We tested the role of the molecular clock in adult cardiomyocytes by generating mice that allow for the inducible cardiomyocyte-specific deletion of Bmal1 (iCSΔBmal1). ECG telemetry showed that cardiomyocyte-specific deletion of Bmal1 (iCSΔBmal1(-/-)) in adult mice slowed heart rate, prolonged RR and QRS intervals, and increased episodes of arrhythmia. Moreover, isolated iCSΔBmal1(-/-) hearts were more susceptible to arrhythmia during electromechanical stimulation. Examination of candidate cardiac ion channel genes showed that Scn5a, which encodes the principle cardiac voltage-gated Na(+) channel (Na(V)1.5), was circadianly expressed in control mouse and rat hearts but not in iCSΔBmal1(-/-) hearts. In vitro studies confirmed circadian expression of a human Scn5a promoter-luciferase reporter construct and determined that overexpression of clock factors transactivated the Scn5a promoter. Loss of Scn5a circadian expression in iCSΔBmal1(-/-) hearts was associated with decreased levels of Na(V)1.5 and Na(+) current in ventricular myocytes. We conclude that disruption of the molecular clock in the adult heart slows heart rate, increases arrhythmias, and decreases the functional expression of Scn5a. These findings suggest a potential link between environmental factors that alter the cardiomyocyte molecular clock and factors that influence arrhythmia susceptibility in humans.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.