The calcineurin pathway links hyperpolarization (Kir2.1)-induced Ca super(2+) signals to human myoblast differentiation and fusion

• Published in: Development (Cambridge) Vol. 133; no. 16; pp. 3107 - 3114
• Main Authors: Konig, Stephane, Beguet, Anne, Bader, Charles R, Bernheim, Laurent
• Format: Journal Article
• Language: English
• Published: 01.08.2006
• ISSN: 0950-1991; 1477-9129

In human myoblasts triggered to differentiate, a hyperpolarization, resulting from K super(+) channel (Kir2.1) activation, allows the generation of an intracellular Ca super(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 super(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 super(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.