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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The calcineurin pathway links hyperpolarization (Kir2.1)-induced Ca2+ signals to human myoblast differentiation and fusion.

In human myoblasts triggered to differentiate, a hyperpolarization, resulting from K(+) channel (Kir2.1) activation, allows the generation of an intracellular Ca(2+) signal. This signal induces an increase in expression/activity of two key transcription factors of the differentiation process, myogenin and MEF2. Blocking hyperpolarization inhibits myoblast differentiation. The link between hyperpolarization-induced Ca(2+) signals and the four main regulatory pathways involved in myoblast differentiation was the object of this study. Of the calcineurin, p38- MAPK, PI3K and CaMK pathways, only the calcineurin pathway was inhibited when Kir2.1-linked hyperpolarization was blocked. The CaMK pathway, although Ca(2+) dependent, is unaffected by changes in membrane potential or block of Kir2.1 channels. Concerning the p38- MAPK and PI3K pathways, their activity is present already in proliferating myoblasts and they are unaffected by hyperpolarization or Kir2.1 channel block. We conclude that the Kir2.1-induced hyperpolarization triggers human myoblast differentiation via the activation of the calcineurin pathway, which, in turn, induces expression/activity of myogenin and MEF2.[1]


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