Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

Myofilament Ca2+ sensitization causes susceptibility to cardiac arrhythmia in mice
Franz Baudenbacher, … , James D. Potter, Björn C. Knollmann
Franz Baudenbacher, … , James D. Potter, Björn C. Knollmann
Published November 20, 2008
Citation Information: J Clin Invest. 2008;118(12):3893-3903. https://doi.org/10.1172/JCI36642.
View: Text | PDF
Research Article Article has an altmetric score of 1

Myofilament Ca2+ sensitization causes susceptibility to cardiac arrhythmia in mice

  • Text
  • PDF
Abstract

In human cardiomyopathy, anatomical abnormalities such as hypertrophy and fibrosis contribute to the risk of ventricular arrhythmias and sudden death. Here we have shown that increased myofilament Ca2+ sensitivity, also a common feature in both inherited and acquired human cardiomyopathies, created arrhythmia susceptibility in mice, even in the absence of anatomical abnormalities. In mice expressing troponin T mutants that cause hypertrophic cardiomyopathy in humans, the risk of developing ventricular tachycardia was directly proportional to the degree of Ca2+ sensitization caused by the troponin T mutation. Arrhythmia susceptibility was reproduced with the Ca2+-sensitizing agent EMD 57033 and prevented by myofilament Ca2+ desensitization with blebbistatin. Ca2+ sensitization markedly changed the shape of ventricular action potentials, resulting in shorter effective refractory periods, greater beat-to-beat variability of action potential durations, and increased dispersion of ventricular conduction velocities at fast heart rates. Together these effects created an arrhythmogenic substrate. Thus, myofilament Ca2+ sensitization represents a heretofore unrecognized arrhythmia mechanism. The protective effect of blebbistatin provides what we believe to be the first direct evidence that reduction of Ca2+ sensitivity in myofilaments is antiarrhythmic and might be beneficial to individuals with hypertrophic cardiomyopathy.

Authors

Franz Baudenbacher, Tilmann Schober, Jose Renato Pinto, Veniamin Y. Sidorov, Fredrick Hilliard, R. John Solaro, James D. Potter, Björn C. Knollmann

×

Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 Total
Citations: 1 5 10 8 10 5 7 11 18 12 9 13 5 11 13 15 6 1 160
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2018 (11)

Title and authors Publication Year
Calcium in Brugada Syndrome: Questions for Future Research
MM Monasky, C Pappone, M Piccoli, A Ghiroldi, E Micaglio, L Anastasia
Frontiers in physiology 2018
Translating emerging molecular genetic insights into clinical practice in inherited cardiomyopathies
B Asatryan, A Medeiros-Domingo
Journal of Molecular Medicine 2018
Treatments targeting inotropy
C Maack, T Eschenhagen, N Hamdani, FR Heinzel, AR Lyon, DJ Manstein, J Metzger, Z Papp, CG Tocchetti, MB Yilmaz, SD Anker, JL Balligand, J Bauersachs, D Brutsaert, L Carrier, S Chlopicki, JG Cleland, RA de Boer, A Dietl, R Fischmeister, VP Harjola, S Heymans, D Hilfiker-Kleiner, J Holzmeister, G de Keulenaer, G Limongelli, WA Linke, LH Lund, J Masip, M Metra, C Mueller, B Pieske, P Ponikowski, A Ristić, F Ruschitzka, PM Seferović, H Skouri, WH Zimmermann, A Mebazaa
European Heart Journal 2018
Altered Ca2+ and Na+ Homeostasis in Human Hypertrophic Cardiomyopathy: Implications for Arrhythmogenesis
R Coppini, C Ferrantini, A Mugelli, C Poggesi, E Cerbai
Frontiers in physiology 2018
Transverse cardiac slicing and optical imaging for analysis of transmural gradients in membrane potential and Ca 2+ transients in murine heart: Murine cardiac slice optical imaging
Q Wen, K Gandhi, RA Capel, G Hao, C O'Shea, G Neagu, S Pearcey, D Pavlovic, DA Terrar, J Wu, G Faggian, P Camelliti, M Lei
The Journal of Physiology 2018
Hypertrophic cardiomyopathy-linked mutation in troponin T causes myofibrillar disarray and pro-arrhythmic action potential changes in human iPSC cardiomyocytes
L Wang, K Kim, S Parikh, AG Cadar, KR Bersell, H He, JR Pinto, DO Kryshtal, BC Knollmann
Journal of Molecular and Cellular Cardiology 2018
Cardiomyopathy phenotypes in human-induced pluripotent stem cell-derived cardiomyocytes—a systematic review
T Eschenhagen, L Carrier
Pflügers Archiv - European Journal of Physiology 2018
Hypertrophic cardiomyopathy: Sudden cardiac death risk stratification in adults
P Jordà, A García-Álvarez
Global Cardiology Science and Practice 2018
Structural and functional impact of troponin C-mediated Ca2+ sensitization on myofilament lattice spacing and cross-bridge mechanics in mouse cardiac muscle
D Gonzalez-Martinez, JR Johnston, M Landim-Vieira, W Ma, O Antipova, O Awan, TC Irving, PB Chase, JR Pinto
Journal of Molecular and Cellular Cardiology 2018
Risk stratification in pediatric hypertrophic cardiomyopathy: Insights for bridging the evidence gap?
SJ Nakano, SC Menon
Progress in Pediatric Cardiology 2018
Increased Vulnerability to Atrial Fibrillation Is Associated With Increased Susceptibility to Alternans in Old Sheep
CM Pearman, GW Madders, EJ Radcliffe, GJ Kirkwood, M Lawless, A Watkins, CE Smith, AW Trafford, DA Eisner, KM Dibb
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease 2018

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Highlighted by 1 platforms
206 readers on Mendeley
See more details