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Interventricular differences in myofilament function in experimental congestive heart failure

  • Cardiovascular Physiology
  • Published:
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Abstract

This study was conducted to identify molecular mechanisms which explain interventricular differences in myofilament function in experimental congestive heart failure (CHF). CHF was induced in rats by chronic aortic banding or myocardial infarction for 32–36 weeks. Right and left ventricular (RV, LV) myocytes were mechanically isolated, triton-skinned, and attached to a force transducer and motor arm. Myofilament force–[Ca2+] relations assessed maximal Ca2+-saturated force (F max) and the [Ca2+] at 50% of F max (EC50). Myofilament protein phosphorylation was determined via ProQ diamond phospho-staining. Protein kinase C (PKC)-α expression/activation and site-specific phosphorylation of cardiac troponin I (cTnI) and cardiac troponin T (cTnT) were measured via immunoblotting. Relative to controls, failing RV myocytes displayed a ~45% decrease in F max with no change in EC50, whereas failing LV myocytes displayed a ~45% decrease in F max and ~50% increase in EC50. Failing LV myofilaments were less Ca2+-sensitive (37% increase in EC50) than failing RV myofilaments. Expression and activation of PKC-α was increased twofold in failing RV myocardium and relative to the RV, PKC-α was twofold higher in the failing LV, while PKC-β expression was unchanged by CHF. PKC-α-dependent phosphorylation and PP1-mediated dephosphorylation of failing RV myofilaments increased EC50 and increased F max, respectively. Phosphorylation of cTnI and cTnT was greater in failing LV myofilaments than in failing RV myofilaments. RV myofilament function is depressed in experimental CHF in association with increased PKC-α signaling and myofilament protein phosphorylation. Furthermore, myofilament dysfunction is greater in the LV compared to the RV due in part to increased PKC-α activation and phosphorylation of cTnI and cTnT.

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Acknowledgments

This work was supported by NIH grants HL64035, HL77195, HL62426, AG032009, and T32-007692 and the American Heart Association (0335199 N, 0230038 N). RJB was supported by a United Negro College Fund-MERCK Predoctoral Fellowship and American Physiological Society Porter Physiology Fellowship.

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Authors and Affiliations

  1. Department of Physiology & Biophysics, Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, IL, USA

    Rashad J. Belin, David L. Geenen, R. John Solaro & Pieter P. de Tombe

  2. Department of Physiology, University of Kentucky, Lexington, KY, USA

    Marius P. Sumandea, Gail A. Sievert & Laura A. Harvey

  3. Department of Cell and Molecular Physiology, Loyola University, Chicago, IL, USA

    Pieter P. de Tombe

  4. Department of Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, 2160 South First Ave., Maywood, IL, 60153, USA

    Pieter P. de Tombe

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  1. Rashad J. Belin
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  2. Marius P. Sumandea
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  3. Gail A. Sievert
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  4. Laura A. Harvey
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  5. David L. Geenen
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  7. Pieter P. de Tombe
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Correspondence to Pieter P. de Tombe.

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Belin, R.J., Sumandea, M.P., Sievert, G.A. et al. Interventricular differences in myofilament function in experimental congestive heart failure. Pflugers Arch - Eur J Physiol 462, 795–809 (2011). https://doi.org/10.1007/s00424-011-1024-4

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  • DOI: https://doi.org/10.1007/s00424-011-1024-4

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