Journal Article

Enhanced excitation-coupled Ca<sup>2+</sup> entry induces nuclear translocation of NFAT and contributes to IL-6 release from myotubes from patients with central core disease

Susan Treves, Mirko Vukcevic, Pierre-Yves Jeannet, Soledad Levano, Thierry Girard, Albert Urwyler, Dirk Fischer, Thomas Voit, Heinz Jungbluth, Sue Lillis, Francesco Muntoni, Ros Quinlivan, Anna Sarkozy, Kate Bushby and Francesco Zorzato

in Human Molecular Genetics

Volume 20, issue 3, pages 589-600
Published in print February 2011 | ISSN: 0964-6906
Published online November 2010 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddq506
Enhanced excitation-coupled Ca2+ entry induces nuclear translocation of NFAT and contributes to IL-6 release from myotubes from patients with central core disease

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Prolonged depolarization of skeletal muscle cells induces entry of extracellular calcium into muscle cells, an event referred to as excitation-coupled calcium entry. Skeletal muscle excitation-coupled calcium entry relies on the interaction between the 1,4-dihydropyridine receptor on the sarcolemma and the ryanodine receptor on the sarcoplasmic reticulum membrane. In this study, we directly measured excitation-coupled calcium entry by total internal reflection fluorescence microscopy in human skeletal muscle myotubes harbouring mutations in the RYR1 gene linked to malignant hyperthermia (MH) and central core disease (CCD). We found that excitation-coupled calcium entry is strongly enhanced in cells from patients with CCD compared with individuals with MH and controls. Furthermore, excitation-coupled calcium entry induces generation of reactive nitrogen species and enhances nuclear localization of NFATc1, which in turn may be responsible for the increased IL-6 released by myotubes from patients with CCD.

Journal Article.  7508 words.  Illustrated.

Subjects: Genetics and Genomics

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