Within skeletal muscles, myogenic stem cells - satellite cells - will proliferate and then, differentiate to build/re-build muscle fibers. In vitro, myoblasts derived from human satellite cells can be induced to differentiate after medium switch. Using this cellular model, we previously showed that one of the first steps of myoblast differentiation is a hyperpolarization of myoblasts' membrane. This change of membrane potential is followed by a calcium entry and the expression of myogenic transcription factors. More precisely, myoblast hyperpolarization relies on a potassium channel, Kir2.1 which is maintained inactive during proliferation. Here, EGF receptor, was identified as a stimulator of proliferation and an inhibitor of differentiation. EGFR expression is physiologically regulated in myoblasts and decreases during differentiation, in particular via the proteasome. Absence of EGFR results in a decrease of Kir2.1 phosphorylation, activation of this channel favoring calcium entry, expression of muscle-specific transcription factors and proteins.