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Myoscape controls cardiac calcium cycling and contractility via regulation of L-type calcium channel surface expression

Nature Communications, ISSN: 2041-1723, Vol: 7, Issue: 1
2016
  • 20
    Citations
  • 0
    Usage
  • 42
    Captures
  • 1
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    20
    • Citation Indexes
      20
  • Captures
    42
  • Mentions
    1
    • References
      1
      • 1

Article Description

Calcium signalling plays a critical role in the pathogenesis of heart failure. Here we describe a cardiac protein named Myoscape/FAM40B/STRIP2, which directly interacts with the L-type calcium channel. Knockdown of Myoscape in cardiomyocytes decreases calcium transients associated with smaller Ca amplitudes and a lower diastolic Ca content. Likewise, L-type calcium channel currents are significantly diminished on Myoscape ablation, and downregulation of Myoscape significantly reduces contractility of cardiomyocytes. Conversely, overexpression of Myoscape increases global Ca transients and enhances L-type Ca channel currents, and is sufficient to restore decreased currents in failing cardiomyocytes. In vivo, both Myoscape-depleted morphant zebrafish and Myoscape knockout (KO) mice display impairment of cardiac function progressing to advanced heart failure. Mechanistically, Myoscape-deficient mice show reduced L-type Cacurrents, cell capacity and calcium current densities as a result of diminished LTCC surface expression. Finally, Myoscape expression is reduced in hearts from patients suffering of terminal heart failure, implying a role in human disease.

Bibliographic Details

Matthias Eden; Norbert Frey; Alexander Bernt; Ashraf Rangrez; Benjamin Meder; Mirko Völkers; Rainer Will; Matthias Busch; Raffi Bekeredjian; Hugo Katus; Patrick Most; Montatip Poomvanicha; Katrin Domes; Franz Hofmann; M. Branchereau; P. Marck; Thomas Klopstock; Christophe Heymes; Martin Hrabě de Angelis; Wolfgang Rottbauer; Thure Adler; Dirk H. Busch; Juan Antonio Aguilar-Pimentel; Alexander Götz; Cornelia Prehn; Jerzy Adamski; Lore Becker; Marion Horsch; Johannes Beckers; Anja Schrewe; Lillian Garrett; Sabine M. Hölter; Oliver Puk; Wolfgang Hans; Jan Rozman; Frauke Neff; Monica Tost; Julia Calzada-Wack; Tanja Klein-Rodewald; Ildikó Rácz; Birgit Rathkolb; Christoph Lengger; Holger Maier; Claudia Stoeger; Stefanie Leuchtenberger; Valéri Gailus-Durner; Helmut Fuchs; Markus Ollert; Holger Schulz; Eckhard Wolf; Wolfgang Wurst; Jochen Graw; Martin Klingenspor; Andreas Zimmer

Springer Science and Business Media LLC

Chemistry; Biochemistry, Genetics and Molecular Biology; Physics and Astronomy

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