ArticleBritish journal of pharmacology2016
A novel transgenic rabbit model with reduced repolarization reserve: long QT syndrome caused by a dominant-negative mutation of the KCNE1 gene.
Article in British journal of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 43 citations in OpenAlex.
- Functional Profiling ofCirculation. Genomic and precision medicine · 2025Article
- New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.Scientific reports · 2023Article
- ActionPytential: An open source tool for analyzing and visualizing cardiac action potential data.Heliyon · 2023Article
- A Possible Explanation for the Low Penetrance of Pathogenic KCNE1 Variants in Long QT Syndrome Type 5.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Animal Models to Study Cardiac Arrhythmias.Circulation research · 2022Review
- Docosahexaenoic acid normalizes QT interval in long QT type 2 transgenic rabbit models in a genotype-specific fashion.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 · 2022Article
- ESC working group on cardiac cellular electrophysiology position paper: relevance, opportunities, and limitations of experimental models for cardiac electrophysiology research.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 · 2021Review
- A comparative review on heart ion channels, action potentials and electrocardiogram in rodents and human: extrapolation of experimental insights to clinic.Laboratory animal research · 2021Review
- Transgenic LQT2, LQT5, and LQT2-5 rabbit models with decreased repolarisation reserve for prediction of drug-induced ventricular arrhythmias.British journal of pharmacology · 2020Article
- Transgenic Rabbit Models in Proarrhythmia Research.Frontiers in pharmacology · 2020Review
- Definition of hidden drug cardiotoxicity: paradigm change in cardiac safety testing and its clinical implications.European heart journal · 2019Review
- The genetic architecture of long QT syndrome: A critical reappraisal.Trends in cardiovascular medicine · 2018Review
- Low Resting Membrane Potential and Low Inward Rectifier Potassium Currents Are Not Inherent Features of hiPSC-Derived Cardiomyocytes.Stem cell reports · 2018Article
- The anaesthetized rabbit with acute atrioventricular block provides a new model for detecting drug-induced Torsade de Pointes.British journal of pharmacology · 2017Article
- Monitoring of Venus transgenic cell migration during pregnancy in non-transgenic rabbits.Transgenic research · 2017Article
- Potassium currents in the heart: functional roles in repolarization, arrhythmia and therapeutics.The Journal of physiology · 2017Review
- Zingerone alleviates the delayed ventricular repolarization and AV conduction in diabetes: Effect on cardiac fibrosis and inflammation.PloS one · 2017Article
- Species-Dependent Mechanisms of Cardiac Arrhythmia: A Cellular Focus.Clinical Medicine Insights. Cardiology · 2017Review
- A novel transgenic rabbit model with reduced repolarization reserve: long QT syndrome caused by a dominant-negative mutation of the KCNE1 gene.British journal of pharmacology · 2016Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe reliable assessment of proarrhythmic risk of compounds under development remains an elusive goal. Current safety guidelines focus on the effects of blocking the KCNH2/HERG ion channel-in tissues and animals with intact repolarization. Novel models with better predictive value are needed that more closely reflect the conditions in patients with cardiac remodelling and reduced repolarization reserve. EXPERIMENTAL APPROACH: We have developed a model for the long QT syndrome type-5 in rabbits (LQT5 ) with cardiac-specific overexpression of a mutant (G52R) KCNE1 β-subunit of the channel that carries the slow delayed-rectifier K(+) -current (IKs ). ECG parameters, including short-term variability of the QT interval (STVQT ), a biomarker for proarrhythmic risk, and arrhythmia development were recorded. In vivo, arrhythmia susceptibility was evaluated by i.v. administration of the IKr blocker dofetilide. K(+) currents were measured with the patch-clamp technique. KEY
resultsPatch-clamp studies in ventricular myocytes isolated from LQT5 rabbits revealed accelerated IKs and IKr deactivation kinetics. At baseline, LQT5 animals exhibited slightly but significantly prolonged heart-rate corrected QT index (QTi) and increased STVQT . Dofetilide provoked Torsade-de-Pointes arrhythmia in a greater proportion of LQT5 rabbits, paralleled by a further increase in STVQT . CONCLUSION AND IMPLICATIONS: We have created a novel transgenic LQT5 rabbit model with increased susceptibility to drug-induced arrhythmias that may represent a useful model for testing proarrhythmic potential and for investigations of the mechanisms underlying arrhythmias and sudden cardiac death due to repolarization disturbances.
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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.