ArticleCirculation research2016
Microdomain-Specific Modulation of L-Type Calcium Channels Leads to Triggered Ventricular Arrhythmia in Heart Failure.
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Article in Circulation research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
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74citing papers in PubMed, 1 pooled it
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Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- Association of Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2i) with Cardiac Arrhythmias: A Systematic Review and Meta-Analysis of Cardiovascular Outcome Trials.Reviews in cardiovascular medicine · 2023Pooled it
- The Hodgkin-Huxley-Katz Prize Lecture: Heart digital twins: A new paradigm in arrhythmia medicine.The Journal of physiology · 2026Article
- Exploring the role of CaMKII in exercise-induced cardioprotection.Human cell · 2026Review
- Loss of caveolar A1 adenosine receptor signalling blunts anti-adrenergic control in heart failure.Cardiovascular research · 2026Article
- Downregulation of L-type CaHeart rhythm · 2026Article
- Phosphoinositide Depletion and Compensatory Phospho-Signaling in Angiotensin II-Induced Heart Disease.Circulation research · 2026Article
- Review
- Cardiac Cell Remodeling in Obesity and Diabetes.Handbook of experimental pharmacology · 2026Review
- Aberrant myocardial calcium cycling: pathogenic mechanisms and targeted therapeutics for heart failure.Frontiers in cardiovascular medicine · 2026Review
- Targeting Calcium Regulation for Heart Failure and Arrhythmia Therapeutics: A Critical Review.Circulation · 2025Review
- Stretch regulation of β2-Adrenoceptor signalling in cardiomyocytes requires caveolae.Cardiovascular research · 2025Article
- From function to structure: how myofibrillogenesis influences the transverse-axial tubular system development and its peculiarities.Frontiers in physiology · 2025Review
- Computational modeling of cardiac electrophysiology and arrhythmogenesis: toward clinical translation.Physiological reviews · 2024Review
- Dynamic Changes in Ion Channels during Myocardial Infarction and Therapeutic Challenges.International journal of molecular sciences · 2024Review
- Relationship between ion currents and membrane capacitance in canine ventricular myocytes.Scientific reports · 2024Article
- Optogenetic Modulation of Arrhythmia Triggers: Proof-of-Concept from Computational Modeling.Cellular and molecular bioengineering · 2023Article
- Diversity of cells and signals in the cardiovascular system.The Journal of physiology · 2023Article
- Review
- Design and Applications of Genetically-Encoded Voltage-Dependent Calcium Channel Inhibitors.Handbook of experimental pharmacology · 2023Review
- β subunits of voltage-gated calcium channels in cardiovascular diseases.Frontiers in cardiovascular medicine · 2023Review
14 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 3 countries.
Jose L Sanchez-AlonsoFrom the Department of Cardiovascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute (J.L.S.-A., A.B., A.V.G., S.S., N.B., M.B.S., C.M., A.R.L., P.P.P., J.G.), Department of Medicine (Y.E.K.), and Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute (P.P.P.), Imperial College London, United Kingdom; Department of Biomedical Engineering and Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O., N.A.T.); NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (A.R.L.); Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (S.S., V.O.N.); and Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Telangana, India (A.B.).
Anamika BhargavaFrom the Department of Cardiovascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute (J.L.S.-A., A.B., A.V.G., S.S., N.B., M.B.S., C.M., A.R.L., P.P.P., J.G.), Department of Medicine (Y.E.K.), and Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute (P.P.P.), Imperial College London, United Kingdom; Department of Biomedical Engineering and Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O., N.A.T.); NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (A.R.L.); Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (S.S., V.O.N.); and Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Telangana, India (A.B.).
Thomas O'HaraFrom the Department of Cardiovascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute (J.L.S.-A., A.B., A.V.G., S.S., N.B., M.B.S., C.M., A.R.L., P.P.P., J.G.), Department of Medicine (Y.E.K.), and Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute (P.P.P.), Imperial College London, United Kingdom; Department of Biomedical Engineering and Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O., N.A.T.); NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (A.R.L.); Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (S.S., V.O.N.); and Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Telangana, India (A.B.).
Alexey V GlukhovFrom the Department of Cardiovascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute (J.L.S.-A., A.B., A.V.G., S.S., N.B., M.B.S., C.M., A.R.L., P.P.P., J.G.), Department of Medicine (Y.E.K.), and Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute (P.P.P.), Imperial College London, United Kingdom; Department of Biomedical Engineering and Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O., N.A.T.); NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (A.R.L.); Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (S.S., V.O.N.); and Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Telangana, India (A.B.).
Sophie SchobesbergerFrom the Department of Cardiovascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute (J.L.S.-A., A.B., A.V.G., S.S., N.B., M.B.S., C.M., A.R.L., P.P.P., J.G.), Department of Medicine (Y.E.K.), and Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute (P.P.P.), Imperial College London, United Kingdom; Department of Biomedical Engineering and Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O., N.A.T.); NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (A.R.L.); Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (S.S., V.O.N.); and Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Telangana, India (A.B.).
Navneet BhogalFrom the Department of Cardiovascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute (J.L.S.-A., A.B., A.V.G., S.S., N.B., M.B.S., C.M., A.R.L., P.P.P., J.G.), Department of Medicine (Y.E.K.), and Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute (P.P.P.), Imperial College London, United Kingdom; Department of Biomedical Engineering and Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O., N.A.T.); NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (A.R.L.); Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (S.S., V.O.N.); and Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Telangana, India (A.B.).
Markus B SikkelFrom the Department of Cardiovascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute (J.L.S.-A., A.B., A.V.G., S.S., N.B., M.B.S., C.M., A.R.L., P.P.P., J.G.), Department of Medicine (Y.E.K.), and Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute (P.P.P.), Imperial College London, United Kingdom; Department of Biomedical Engineering and Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O., N.A.T.); NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (A.R.L.); Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (S.S., V.O.N.); and Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Telangana, India (A.B.).
Catherine MansfieldFrom the Department of Cardiovascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute (J.L.S.-A., A.B., A.V.G., S.S., N.B., M.B.S., C.M., A.R.L., P.P.P., J.G.), Department of Medicine (Y.E.K.), and Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute (P.P.P.), Imperial College London, United Kingdom; Department of Biomedical Engineering and Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O., N.A.T.); NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (A.R.L.); Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (S.S., V.O.N.); and Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Telangana, India (A.B.).
Yuri E KorchevFrom the Department of Cardiovascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute (J.L.S.-A., A.B., A.V.G., S.S., N.B., M.B.S., C.M., A.R.L., P.P.P., J.G.), Department of Medicine (Y.E.K.), and Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute (P.P.P.), Imperial College London, United Kingdom; Department of Biomedical Engineering and Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O., N.A.T.); NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (A.R.L.); Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (S.S., V.O.N.); and Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Telangana, India (A.B.).
Alexander R LyonFrom the Department of Cardiovascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute (J.L.S.-A., A.B., A.V.G., S.S., N.B., M.B.S., C.M., A.R.L., P.P.P., J.G.), Department of Medicine (Y.E.K.), and Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute (P.P.P.), Imperial College London, United Kingdom; Department of Biomedical Engineering and Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O., N.A.T.); NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (A.R.L.); Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (S.S., V.O.N.); and Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Telangana, India (A.B.).
Prakash P PunjabiFrom the Department of Cardiovascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute (J.L.S.-A., A.B., A.V.G., S.S., N.B., M.B.S., C.M., A.R.L., P.P.P., J.G.), Department of Medicine (Y.E.K.), and Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute (P.P.P.), Imperial College London, United Kingdom; Department of Biomedical Engineering and Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O., N.A.T.); NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (A.R.L.); Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (S.S., V.O.N.); and Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Telangana, India (A.B.).
Viacheslav O NikolaevFrom the Department of Cardiovascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute (J.L.S.-A., A.B., A.V.G., S.S., N.B., M.B.S., C.M., A.R.L., P.P.P., J.G.), Department of Medicine (Y.E.K.), and Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute (P.P.P.), Imperial College London, United Kingdom; Department of Biomedical Engineering and Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O., N.A.T.); NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (A.R.L.); Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (S.S., V.O.N.); and Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Telangana, India (A.B.).
Natalia A TrayanovaFrom the Department of Cardiovascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute (J.L.S.-A., A.B., A.V.G., S.S., N.B., M.B.S., C.M., A.R.L., P.P.P., J.G.), Department of Medicine (Y.E.K.), and Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute (P.P.P.), Imperial College London, United Kingdom; Department of Biomedical Engineering and Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O., N.A.T.); NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (A.R.L.); Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (S.S., V.O.N.); and Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Telangana, India (A.B.).
Julia GorelikFrom the Department of Cardiovascular Sciences, Imperial Centre for Translational and Experimental Medicine, National Heart and Lung Institute (J.L.S.-A., A.B., A.V.G., S.S., N.B., M.B.S., C.M., A.R.L., P.P.P., J.G.), Department of Medicine (Y.E.K.), and Department of Cardiothoracic Surgery, Hammersmith Hospital, National Heart and Lung Institute (P.P.P.), Imperial College London, United Kingdom; Department of Biomedical Engineering and Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD (T.O., N.A.T.); NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (A.R.L.); Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (S.S., V.O.N.); and Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Telangana, India (A.B.). j.gorelik@imperial.ac.uk.
University Medical Center Hamburg-Eppendorf · DEUniversität Hamburg · DEJohns Hopkins University · USRoyal Brompton Hospital · GBNIHR Royal Brompton Cardiovascular Biomedical Research Unit · GB
Funding
Exploration of Arrhythmogenic Triggers and Substrates in Heart FailureR01HL126802 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI EFIMOV, IGOR R, GORELIK, JULIA · 2016 to 2019
$2.8MBritish Heart Foundation RG/12/18/30088Medical Research Council MR/L006855/1NHLBI NIH HHS R01 HL126802
Abstract
rationaleDisruption in subcellular targeting of Ca(2+) signaling complexes secondary to changes in cardiac myocyte structure may contribute to the pathophysiology of a variety of cardiac diseases, including heart failure (HF) and certain arrhythmias.
objectiveTo explore microdomain-targeted remodeling of ventricular L-type Ca(2+) channels (LTCCs) in HF. METHODS AND
resultsSuper-resolution scanning patch-clamp, confocal and fluorescence microscopy were used to explore the distribution of single LTCCs in different membrane microdomains of nonfailing and failing human and rat ventricular myocytes. Disruption of membrane structure in both species led to the redistribution of functional LTCCs from their canonical location in transversal tubules (T-tubules) to the non-native crest of the sarcolemma, where their open probability was dramatically increased (0.034±0.011 versus 0.154±0.027, P<0.001). High open probability was linked to enhance calcium-calmodulin kinase II-mediated phosphorylation in non-native microdomains and resulted in an elevated ICa,L window current, which contributed to the development of early afterdepolarizations. A novel model of LTCC function in HF was developed; after its validation with experimental data, the model was used to ascertain how HF-induced T-tubule loss led to altered LTCC function and early afterdepolarizations. The HF myocyte model was then implemented in a 3-dimensional left ventricle model, demonstrating that such early afterdepolarizations can propagate and initiate reentrant arrhythmias.
conclusionsMicrodomain-targeted remodeling of LTCC properties is an important event in pathways that may contribute to ventricular arrhythmogenesis in the settings of HF-associated remodeling. This extends beyond the classical concept of electric remodeling in HF and adds a new dimension to cardiovascular disease.
Indexed as
AdultAgedAnimalsArrhythmias, CardiacCalcium Channels, L-TypeCells, CulturedFemaleHeart FailureHumansMaleMembrane MicrodomainsMiddle AgedMyocytes, CardiacRatsRats, Sprague-DawleyCalcium Channels, L-Typeelectrophysiologyheart failureL-type calcium channelmembrane microdomainsmyocardial infarction
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