ArticleJournal of the American Heart Association2013
Increased expression of HCN channels in the ventricular myocardium contributes to enhanced arrhythmicity in mouse failing hearts.
Article in Journal of the American Heart Association, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 78 citations in OpenAlex.
- The Evolving Role of Ivabradine for Focal Atrial Tachycardia: A Systematic Review.Journal of arrhythmia · 2026Article
- Antisense Oligonucleotide Therapeutics Targeting Age-Related Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Meta-analysis of genome-wide association studies of doxorubicin-induced arrhythmia identifiesmedRxiv : the preprint server for health sciences · 2025Article
- Review
- Tumour necrosis factor alpha-induced protein 3-interacting protein 3 overexpression protects against arrhythmogenic remodelling in the heart failure mice.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2024Article
- Increased GIRK channel activity prevents arrhythmia in mice with heart failure by enhancing ventricular repolarization.Scientific reports · 2023Article
- The effect of ivabradine therapy on dilated cardiomyopathy patients with congestive heart failure: a systematic review and meta-analysis.Frontiers in cardiovascular medicine · 2023Review
- Effect of ivabradine on ventricular arrhythmias in heart failure patients with reduced ejection fraction.Revista da Associacao Medica Brasileira (1992) · 2023Article
- Slowing Heart Rate Protects Against Pathological Cardiac Hypertrophy.Function (Oxford, England) · 2023Article
- Heart failure in mice induces a dysfunction of the sinus node associated with reduced CaMKII signaling.The Journal of general physiology · 2022Article
- NRSF/REST-Mediated Epigenomic Regulation in the Heart: Transcriptional Control of Natriuretic Peptides and Beyond.Biology · 2022Review
- Article
- Caveolin-3 and Arrhythmias: Insights into the Molecular Mechanisms.Journal of clinical medicine · 2022Review
- Review: HCN Channels in the Heart.Current cardiology reviews · 2022Review
- Molecular Remodeling of Cardiac Sinus Node Associated with Acute Chagas Disease Myocarditis.Microorganisms · 2021Article
- Effect of Ivabradine on Cardiac Ventricular Arrhythmias: Friend or Foe?Journal of clinical medicine · 2021Review
- Cardiomyocyte-specific deletion of β-catenin protects mouse hearts from ventricular arrhythmias after myocardial infarction.Scientific reports · 2021Article
- Isolated downregulation of HCN2 in ventricles of rats with streptozotocin-induced diabetic cardiomyopathy.BMC cardiovascular disorders · 2021Article
- Reciprocal interaction between IK1 and If in biological pacemakers: A simulation study.PLoS computational biology · 2021Article
- Expression of the pacemaker channel HCN4 in excitatory interneurons in the dorsal horn of the murine spinal cord.Molecular brain · 2020Article
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe efficacy of pharmacological interventions to prevent sudden arrhythmic death in patients with chronic heart failure remains limited. Evidence now suggests increased ventricular expression of hyperpolarization-activated cation (HCN) channels in hypertrophied and failing hearts contributes to their arrythmicity. Still, the role of induced HCN channel expression in the enhanced arrhythmicity associated with heart failure and the capacity of HCN channel blockade to prevent lethal arrhythmias remains undetermined. METHODS AND
resultsWe examined the effects of ivabradine, a specific HCN channel blocker, on survival and arrhythmicity in transgenic mice (dnNRSF-Tg) expressing a cardiac-specific dominant-negative form of neuron-restrictive silencer factor, a useful mouse model of dilated cardiomyopathy leading to sudden death. Ivabradine (7 mg/kg per day orally) significantly reduced ventricular tachyarrhythmias and improved survival among dnNRSF-Tg mice while having no significant effect on heart rate or cardiac structure or function. Ivabradine most likely prevented the increase in automaticity otherwise seen in dnNRSF-Tg ventricular myocytes. Moreover, cardiac-specific overexpression of HCN2 in mice (HCN2-Tg) made hearts highly susceptible to arrhythmias induced by chronic β-adrenergic stimulation. Indeed, ventricular myocytes isolated from HCN2-Tg mice were highly susceptible to β-adrenergic stimulation-induced abnormal automaticity, which was inhibited by ivabradine.
conclusionsHCN channel blockade by ivabradine reduces lethal arrhythmias associated with dilated cardiomyopathy in mice. Conversely, cardiac-specific overexpression of HCN2 channels increases arrhythmogenicity of β-adrenergic stimulation. Our findings demonstrate the contribution of HCN channels to the increased arrhythmicity seen in failing hearts and suggest HCN channel blockade is a potentially useful approach to preventing sudden death in patients with heart failure.
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