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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
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 2016 (12)

Title and authors Publication Year
Murine Electrophysiological Models of Cardiac Arrhythmogenesis
CL Huang
Physiological reviews 2016
Cardiac disease and arrhythmogenesis: Mechanistic insights from mouse models
L Choy, JM Yeo, V Tse, SP Chan, G Tse
IJC Heart & Vasculature 2016
Cardiac troponin structure-function and the influence of hypertrophic cardiomyopathy associated mutations on modulation of contractility
Y Cheng, M Regnier
Archives of Biochemistry and Biophysics 2016
Myocardial energy depletion and dynamic systolic dysfunction in hypertrophic cardiomyopathy
JO Ormerod, MP Frenneaux, MV Sherrid
Nature Reviews Cardiology 2016
Mechanotransduction and Metabolism in Cardiomyocyte Microdomains
FS Pasqualini, AP Nesmith, RE Horton, SP Sheehy, KK Parker
BioMed Research International 2016
TNNT1, TNNT2, and TNNT3: Isoform genes, regulation, and structure–function relationships
B Wei, JP Jin
Gene 2016
Why Is there a Limit to the Changes in Myofilament Ca2+-Sensitivity Associated with Myopathy Causing Mutations?
SB Marston
Frontiers in physiology 2016
Sarcomere neutralization in inherited cardiomyopathy: small-molecule proof-of-concept to correct hyper-Ca 2+ -sensitive myofilaments
BR Thompson, J Martindale, JM Metzger
American journal of physiology. Heart and circulatory physiology 2016
Recent Advances in the Molecular Genetics of Familial Hypertrophic Cardiomyopathy in South Asian Descendants
J Kraker, SK Viswanathan, R Knöll, S Sadayappan
Frontiers in physiology 2016
Epigallocatechin-3-Gallate Accelerates Relaxation and Ca2+ Transient Decay and Desensitizes Myofilaments in Healthy and Mybpc3-Targeted Knock-in Cardiomyopathic Mice
FW Friedrich, F Flenner, M Nasib, T Eschenhagen, L Carrier
Frontiers in physiology 2016
Pre-mRNA mis-splicing of sarcomeric genes in heart failure
C Zhu, Z Chen, W Guo
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 2016
Delineation of Molecular Pathways Involved in Cardiomyopathies Caused by Troponin T Mutations
JE Gilda, X Lai, FA Witzmann, AV Gomes
Molecular & cellular proteomics : MCP 2016

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