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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.
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Research Article Article has an altmetric score of 1

Myofilament Ca2+ sensitization causes susceptibility to cardiac arrhythmia in mice

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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

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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
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Citations to this article in year 2009 (6)

Title and authors Publication Year
Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2009
Mechanical and Energetic Consequences of HCM-Causing Mutations
C Ferrantini, A Belus, N Piroddi, B Scellini, C Tesi, C Poggesi
Journal of Cardiovascular Translational Research 2009
Animal models of arrhythmogenic cardiomyopathy
MD McCauley, XH Wehrens
Disease models & mechanisms 2009
A Functional and Structural Study of Troponin C Mutations Related to Hypertrophic Cardiomyopathy*
JR Pinto, MS Parvatiyar, MA Jones, J Liang, MJ Ackerman, JD Potter
The Journal of biological chemistry 2009
Maintaining cooperation among cardiac myofilament proteins through thick and thin
RJ Solaro
The Journal of Physiology 2009
Characterization of secophalloidin-induced force loss in cardiac myofibrils.
Bukatina AE, Sieck GC, Campbell KB, Belohlavek M
Journal of Muscle Research and Cell Motility 2009

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