Array ( ) PuSH - Publikationsserver des Helmholtz Zentrums München: Myoscape controls cardiac calcium cycling and contractility via regulation of L-type calcium channel surface expression.

PuSH - Publikationsserver des Helmholtz Zentrums München

Eden, M.* ; Meder, B.* ; Völkers, M.* ; Poomvanicha, M.* ; Domes, K.* ; Branchereau, M.* ; Marck, P.* ; Will, R.* ; Bernt, A.* ; Rangrez, A.* ; Busch, M.* ; German Mouse Clinic Consortium (Adler, T. ; Aguilar-Pimentel, J.A. ; Becker, L. ; Beckers, J. ; Busch, D.H. ; Calzada-Wack, J. ; Fuchs, H. ; Gailus-Durner, V. ; Garrett, L. ; Graw, J. ; Götz, A. ; Hans, W. ; Hölter, S.M. ; Horsch, M. ; Klein-Rodewald, T. ; Lengger, C. ; Leuchtenberger, S. ; Maier, H. ; Neff, F. ; Ollert, M. ; Prehn, C. ; Puk, O. ; Rácz, I. ; Rathkolb, B. ; Rozman, J. ; Schrewe, A. ; Schulz, H. ; Stöger, C. ; Tost, M. ; Wurst, W. ; Frey, N.*) ; Hrabě de Angelis, M. ; Heymes, C.* ; Rottbauer, W.* ; Most, P.* ; Hofmann, F.*

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

Nat. Commun. 7:11317 (2016)
Verlagsversion Forschungsdaten DOI
Open Access Gold
Creative Commons Lizenzvertrag
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(2+) amplitudes and a lower diastolic Ca(2+) 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(2+) transients and enhances L-type Ca(2+) 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 Ca(2+)currents, 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Calmodulin Kinase-ii; Ca2+ Channel; Dilated Cardiomyopathy; Heart-failure; Ventricular Myocytes; Failing Human; Adrenergic Regulation; Protein Stability; Ca(v)1.2 Channel; Embryonic Heart
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 7, Heft: , Seiten: , Artikelnummer: 11317 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed