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Decoy calcium channel beta subunits modulate contractile function in myocytes

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Cardiac Cell Biology

Part of the book series: Developments in Molecular and Cellular Biochemistry ((DMCB,volume 39))

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Abstract

To test the hypothesis that mutated β2-subunits of the L-type calcium channel could serve as a decoy and interdict calcium channel trafficking and function, we engineered a β2 subunit that contained the β interaction domain for α1c subunit interaction, but lacked N- and C-terminal domains that might be essential for sarcolemmal localization. An adenoviral vector was constructed containing the gene for the β-interaction domain (BID) fused to green fluorescence protein (GFP), using a vector containing only GFP as control. Freshly plated, dissociated adult rat myocytes were infected and expression and function were assessed at 60 h. Fluorescence microscopy confirmed GFP expression; immunoblot analysis confirmed dose-dependent GFPBID expression. Mechanical properties of adult rat ventricular myocytes were evaluated using a video edge-detection system. Contractility analysis (optical/video, field stimulation) demonstrated that contracting cells decreased from 60 to 2%. Contractile amplitude (percent shortening) decreases significantly from 5.6 vs. 2.4% with no change in time to peak twitch. Recombinant adenovirus overexpressing mutated β2 subunits in adult mammalian myocytes can markedly alter excitation-contraction coupling. This paradigm may offer new approaches to understanding and modulating EC coupling. (Mol Cell Biochem 242: 3–10, 2003)

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Authors and Affiliations

  1. Program in Molecular and Cellular Cardiology, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI, USA

    Q. Ivy Fan, Kathleen M. Vanderpool, Jessica O’Connor & James D. Marsh

  2. Program in Molecular and Cellular Cardiology, Wayne State University School of Medicine, 421 East Canfield Avenue, Detroit, MI, 48201, USA

    James D. Marsh

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  1. Q. Ivy Fan
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  2. Kathleen M. Vanderpool
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  3. Jessica O’Connor
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  4. James D. Marsh
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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

    Elissavet Kardami  & Larry Hryshko  & 

  2. Institute of Cardiovascular Sciences and Division of Stroke and Vascular Disease, St. Boniface General Hospital Research Centre and Department of Physiology, University of Manitoba, Winnipeg, Canada

    Nasrin Mesaeli

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© 2003 Springer Science+Business Media New York

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Fan, Q.I., Vanderpool, K.M., O’Connor, J., Marsh, J.D. (2003). Decoy calcium channel beta subunits modulate contractile function in myocytes. In: Kardami, E., Hryshko, L., Mesaeli, N. (eds) Cardiac Cell Biology. Developments in Molecular and Cellular Biochemistry, vol 39. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-4712-6_1

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  • DOI: https://doi.org/10.1007/978-1-4757-4712-6_1

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-5324-7

  • Online ISBN: 978-1-4757-4712-6

  • eBook Packages: Springer Book Archive

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