Fig. 5. Schematic representation of the role of membrane hyperpolarization during human myoblast differentiation. Chronological illustration of the mechanisms of myoblast differentiation, that begins with calcineurin activation as a consequence of Kir2.1-induced membrane hyperpolarization. Calcineurin activation is strictly associated with Kir2.1 activity and the onset of the differentiation process. Activation of Ca²⁺ influx through T-type Ca²⁺ channels (CaT) or store-operated channels (SOCs), or release of Ca²⁺ for endoplasmic reticulum (stores), could provide the increase of intracellular Ca²⁺ concentration responsible for myoblast differentiation and calcineurin activation (Arnaudeau et al., 2006). However, p38-MAPK, PI3K and CaMK are (or can be) activated during myoblast proliferation without inducing myoblast differentiation. CaMK can be activated by an increase in extracellular Ca²⁺ concentration not linked to the differentiation process. Myogenin and MEF2 expression is observed after calcineurin activation.