Résumé :
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Andersen’s syndrome (AS) is a rare disorder that manifests with a triad: periodic paralysis, cardiac arrhythmia, and development anomalies. Muscle weakness is a feature of this disease that has been reported in two-thirds of the patients. The KCNJ2 gene remains the only gene linked to AS, and encodes for the alpha subunit of the Kir2.1 potassium channel. Several studies have shown that AS mutations lead to a loss of function of the potassium channel activity in vitro. However, in vivo studies on isolated patient myotubes have not been reported. We have performed myotube cultures from muscle biopsies of controls and patients presenting with clinically and genetically defined AS disorder, and our cultures reached 95% of myoblast cells. No morphological difference was observed between AS and control myoblasts at each passage of the cell culture. Cellular proliferation and viability were quantified in parallel with direct cell counts and showed no difference between control and AS patients. It has also been suggested that the alteration in Kir2.1 function would result in impaired myoblast fusion and inhibition of myotube formation (J. Cell Biol. 153:F9-F12). Our data show no significant difference in myoblast fusion index among AS and control patients. Current recordings carried out on differentiated myoblasts from healthy individuals and from AS patients revealed the absence in AS myoblasts of the inwardly rectifying Ba2+-sensitive current. One consequence of the Ik1 loss in the AS myoblasts is a shift of the rest membrane potential towards depolarizing potentials. Our data strongly suggest a loss-of-function of the Kir2.1 channel in ex vivo in AS myoblasts carrying known AS mutations. Our findings describe for the first time the functional consequences of AS mutations in ex vivo differentiated myoblasts and provide the first clues to the periodic paralysis manifestations observed in AS patients.
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