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Modulators of Myofibrillar Function: Implications in Myocardial Failure

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Cardiac Remodeling and Failure

Part of the book series: Progress in Experimental Cardiology ((PREC,volume 5))

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Abstract

In this study, the contribution of key myofibrillar contractile elements in myocardial failure was investigated. Specifically, we assessed the mechanical implications of myosin isoform shifting, troponin T isoform shifting, and troponin I phosphorylation by protein kinase A. The two cardiac myosin isoforms have distinct functional differences which appear to be preserved across mammalian species. V1 cardiac myosin translocates actin filaments 2–3 times faster than V3 myosin but only generates one half the force. Calculated power estimates for the cardiac myosin isoforms are similar. The two adult beef troponin T isoforms have compositional similarities when compared to the two human isoforms differentially expressed in the transition to myocardial failure. Using the in vitro motility assay, no functional differences were elicited between the two isoforms in terms of unloaded shortening, isometric force, calcium sensitivity, or cooperative activation. Lastly, protein kinase A phosphorylation of troponin I resulted in a large increase in the calcium sensitive activation of the thin filament with no change in maximal activation. These results are interpreted in the context of a molecular model of contractile protein function and applied to evolving concepts of the role of the myofibril in myocardial failure.

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Authors and Affiliations

  1. Cardiac Unit, Department of Medicine, University of Vermont, College of Medicine Burlington, Vermont, USA

    Peter VanBuren, Mark Hünlich, David Fishbaugher & Teuro Noguchi

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  1. Peter VanBuren
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  2. Mark Hünlich
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  3. David Fishbaugher
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  4. Teuro Noguchi
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Correspondence to Peter VanBuren .

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Editors and Affiliations

  1. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Pawan K. Singal PhD, DSc (Professor), Ian M. C. Dixon PhD (Associate Professor), Lorrie A. Kirshenbaum PhD (Associate Professor) & Naranjan S. Dhalla PhD, MD (HON), DSc (HON) (Distinguished Professor and Director) (Professor),  (Associate Professor),  (Associate Professor) &  (Distinguished Professor and Director)

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VanBuren, P., Hünlich, M., Fishbaugher, D., Noguchi, T. (2003). Modulators of Myofibrillar Function: Implications in Myocardial Failure. In: Singal, P.K., Dixon, I.M.C., Kirshenbaum, L.A., Dhalla, N.S. (eds) Cardiac Remodeling and Failure. Progress in Experimental Cardiology, vol 5. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9262-8_11

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  • DOI: https://doi.org/10.1007/978-1-4419-9262-8_11

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4864-1

  • Online ISBN: 978-1-4419-9262-8

  • eBook Packages: Springer Book Archive

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