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Reduced cross-bridge dependent stiffness of skinned myocardium from mice lacking cardiac myosin binding protein-C

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Abstract

The role of cardiac myosin binding protein-C (MyBP-C) on myocardial stiffness was examined in skinned papillary muscles of wild-type (WT+/+) and homozygous truncated cardiac MyBP-C (MyBP-Ct/t) male mice. No MyBP-C was detected by gel electrophoresis or by Western blots in the MyBP-Ct/t myocardium. Rigor-bridge dependent myofilament stiffness, i.e., rigor minus relaxed stiffness, in the MyBP-Ct/t myocardium (281 ± 44 kN/m2) was 44% that in WT+/+ (633 ± 141 kN/m2). The center-to-center spacing between thick filaments as determined by X-ray diffraction in MyBP-Ct/t (45.0 ± 1.2 nm) was not significantly different from that in WT+/+ (43.2 ± 0.9 nm). The fraction of cross-sectional area comprised of myofibrils, as determined by electron microscopy, was reduced in the MyBP-Ct/t (39.9%) by 10% compared to WT+/+ (44.5%). These data suggest that the 56% reduction in rigor-bridge dependent stiffness of the skinned MyBP-Ct/t myocardium could not be due solely to a 10% reduction in the number of thick filaments per cross-sectional area and must also be due to approximately 50% reduction in the stiffness of the rigor-bridge attached thick filaments lacking MyBP-C. (Mol Cell Biochem 263: 73–80, 2004)

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Authors and Affiliations

  1. Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT, 05405, USA

    Bradley M. Palmer, Christine E. Seidman, J.G. Seidman, Norman R. Alpert & David W. Maughan

  2. Department of Genetics, Howard Hughes Medical Institute and Harvard Medical School, Boston, MA, 02115, USA

    Bradley K. McConnell & Guo Hua Li

  3. Center for Synchrotron Radiation Research and Instrumentation and Department of Biological, Chemical, and Physical Sciences, Illinois Institute of Technology, Chicago, IL, 60616, USA

    Thomas C. Irving

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  1. Bradley M. Palmer
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  2. Bradley K. McConnell
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  4. Christine E. Seidman
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Palmer, B.M., McConnell, B.K., Li, G.H. et al. Reduced cross-bridge dependent stiffness of skinned myocardium from mice lacking cardiac myosin binding protein-C. Mol Cell Biochem 263, 73–80 (2004). https://doi.org/10.1023/B:MCBI.0000041849.60591.45

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