ArticleJournal of the American Heart Association2015
hERG potassium channel blockade by the HCN channel inhibitor bradycardic agent ivabradine.
Article in Journal of the American Heart Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 83 citations in OpenAlex.
- Reassessing Ivabradine: Potential Benefits and Risks in Atrial Fibrillation Therapy.Cardiovascular drugs and therapy · 2025Review
- Ten-Year Results of a Single-Center Trial Investigating Heart Rate Control with Ivabradine or Metoprolol Succinate in Patients After Heart Transplantation.Journal of cardiovascular development and disease · 2025Article
- Effect of the Membrane Environment on Pharmacologic Inhibition of hERG KJACC. Clinical electrophysiology · 2025Article
- Spinal Nerve Axotomy: Effects on IInternational journal of molecular sciences · 2024Article
- Pacemaker Channels and the Chronotropic Response in Health and Disease.Circulation research · 2024Review
- IThe Journal of physiology · 2023Article
- Inhibition of the hERG Potassium Channel by a Methanesulphonate-Free E-4031 Analogue.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Effect of ivabradine on ventricular arrhythmias in heart failure patients with reduced ejection fraction.Revista da Associacao Medica Brasileira (1992) · 2023Article
- Positive chronotropic action of HCN channel antagonism in human collecting lymphatic vessels.Physiological reports · 2022Article
- No evidence for pericardial restraint in the snapping turtle (American journal of physiology. Regulatory, integrative and comparative physiology · 2022Article
- The Bradycardic Agent Ivabradine Acts as an Atypical Inhibitor of Voltage-Gated Sodium Channels.Frontiers in pharmacology · 2022Article
- Inhibition of the hERG potassium channel by phenanthrene: a polycyclic aromatic hydrocarbon pollutant.Cellular and molecular life sciences : CMLS · 2021Article
- 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
- Ventricular voltage-gated ion channels: Detection, characteristics, mechanisms, and drug safety evaluation.Clinical and translational medicine · 2021Review
- Review
- Bidirectional flow of the funny current (IProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Computational prediction of drug response in short QT syndrome type 1 based on measurements of compound effect in stem cell-derived cardiomyocytes.PLoS computational biology · 2021Article
- Effects of Antiarrhythmic Drugs on hERG Gating in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes From a Patient With Short QT Syndrome Type 1.Frontiers in pharmacology · 2021Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundIvabradine is a specific bradycardic agent used in coronary artery disease and heart failure, lowering heart rate through inhibition of sinoatrial nodal HCN-channels. This study investigated the propensity of ivabradine to interact with KCNH2-encoded human Ether-à-go-go-Related Gene (hERG) potassium channels, which strongly influence ventricular repolarization and susceptibility to torsades de pointes arrhythmia. METHODS AND
resultsPatch clamp recordings of hERG current (IhERG) were made from hERG expressing cells at 37°C. Ih ERG was inhibited with an IC50 of 2.07 μmol/L for the hERG 1a isoform and 3.31 μmol/L for coexpressed hERG 1a/1b. The voltage and time-dependent characteristics of Ih ERG block were consistent with preferential gated-state-dependent channel block. Inhibition was partially attenuated by the N588K inactivation-mutant and the S624A pore-helix mutant and was strongly reduced by the Y652A and F656A S6 helix mutants. In docking simulations to a MthK-based homology model of hERG, the 2 aromatic rings of the drug could form multiple π-π interactions with the aromatic side chains of both Y652 and F656. In monophasic action potential (MAP) recordings from guinea-pig Langendorff-perfused hearts, ivabradine delayed ventricular repolarization and produced a steepening of the MAPD90 restitution curve.
conclusionsIvabradine prolongs ventricular repolarization and alters electrical restitution properties at concentrations relevant to the upper therapeutic range. In absolute terms ivabradine does not discriminate between hERG and HCN channels: it inhibits Ih ERG with similar potency to that reported for native If and HCN channels, with S6 binding determinants resembling those observed for HCN4. These findings may have important implications both clinically and for future bradycardic drug design.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.