Résumé :
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Postnatal myogenesis, which occurs during muscle repair after a lesion, relies on the activation of myogenic stem cells (muscle satellite cells). Activated satellite cells proliferate as myoblasts that have the ability of migrating to the lesion sites where they differentiate and fuse to repair muscle fibers or to create new fibers. The differentiation of myoblast involves withdrawal from the cell cycle, activation of muscle-specific genes, and finally cell fusion yielding a multinucleated myotube. The initiation and the progression through differentiation is a multi-step, calcium-dependent process involving an interplay of several intracellular pathways and myogenic transcription factors expressed at the onset of the differentiation process. Our previous work demonstrated that hyperpolarization of the membrane potential of myoblasts was one of the firsts events to occur. We found that membrane hyperpolarization results from the activation of Kir2.1 inward rectifying potassium channels, and is used by the cell to promote calcium influx through calcium channels. Blockade of potassium or calcium channels inhibits differentiation, indicating that ionic channels are important actors in the differentiation process. In addition, Kir2.1 channels activation precedes myogenin and MEF2 expression, two transcription factors crucial for myoblast differentiation, and also myogenin and MEF2 expression are induced by a Kir2.1-dependent pathway. Recent results suggest (i) that activation of Kir2.1 channels at the onset of differentiation is linked to a tyrosine 242 dephosphorylation of these channels, (ii) that several types of calcium channels (including store-operated calcium channels) can provide the calcium signal required for differentiation to occur, and (iii) that membrane hyperpolarization acts as a molecular switch forcing differentiation through the specific activation of the calcineurin signaling pathway.
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