A role for calcium-calmodulin in regulating nitric oxide production during skeletal muscle satellite cell activation

Ryuichi Tatsumi, Adam L. Wuollet, Kuniko Tabata, Shotaro Nishimura, Shoji Tabata, Wataru Mizunoya, Yoshihide Ikeuchi, Ronald E. Allen

    Research output: Contribution to journalArticlepeer-review

    41 Scopus citations


    When skeletal muscle is stretched or injured, myogenic satellite cells are activated to enter the cell cycle. This process depends on nitric oxide (NO) production by NO synthase (NOS), matrix metalloproteinase activation, release of hepatocyte growth factor (HGF) from the extracellular matrix, and presentation of HGF to the c-met receptor as demonstrated by a primary culture and in vivo assays. We now add evidence that calcium-calmodulin is involved in the satellite cell activation cascade in vitro. Conditioned medium from cultures that were treated with a calcium ionophore (A23187, ionomycin) for 2 h activated cultured satellite cells and contained active HGF, similar to the effect of mechanical stretch or NO donor treatments. The response was abolished by addition of calmodulin inhibitors (calmidazolium, W-13, W-12) or a NOS inhibitor N G-nitro-L-arginine methyl ester hydrochloride but not by its less inactive enantiomer NG-nitro-D-arginine methyl ester hydrochloride. Satellite cells were also shown to express functional calmodulin protein having a calcium-binding activity at 12 h postplating, which is the time at which the calcium ionophore was added in this study and the stretch treatment was applied in our previous experiments. Therefore, results from these experiments provide an additional insight that calcium-calmodulin mediates HGF release from the matrix and that this step in the activation pathway is upstream from NO synthesis.

    Original languageEnglish (US)
    Pages (from-to)C922-C929
    JournalAmerican Journal of Physiology - Cell Physiology
    Issue number4
    StatePublished - Apr 2009


    • Muscle regeneration
    • Stretch-activation

    ASJC Scopus subject areas

    • Physiology
    • Cell Biology


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