title: Mechanisms underlying Andersen's syndrome pathology in skeletal muscle are revealed in human myotubes.
abstract: Andersen's syndrome is a rare disorder that has been defined with a triad: periodic paralysis, cardiac arrhythmia, and development anomalies. Muscle weakness has been reported in two-thirds of the patients. KCNJ2 remains the only gene linked to Andersen's syndrome; this gene encodes for the alpha-subunit of the strong inward-rectifier K+ channel Kir2.1. Several studies have shown that Andersen's syndrome mutations lead to a loss of function of the K+ channel activity in vitro. However, ex vivo studies on isolated patient muscle tissue have not been reported. We have performed muscle biopsies of controls and patients presenting with clinically and genetically defined Andersen's syndrome disorder. Myoblasts were cultured and characterized morphologically and functionally using the whole cell patch-clamp technique. No morphological difference was observed between Andersen's syndrome 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 Andersen's syndrome patients. Moreover, our data show no significant difference in myoblast fusion index among Andersen's syndrome and control patients. Current recordings carried out on myotubes revealed the absence of an inwardly rectifying Ba2+-sensitive current in affected patient cells. One consequence of the Ik1 current loss in Andersen's syndrome myotubes is a shift of the resting membrane potential toward depolarizing potentials. Our data describe for the first time the functional consequences of Andersen's syndrome mutations ex vivo and provide clues to the K+ channel pathophysiology in skeletal muscle.
authors: Centre Hospitalier Universitaire of Nice, Centre de Référence Maladies Neuromusculaires et Sclérose Latérale Amyotrophique, Institut National de la Santé et de la Recherche Médicale Unité 638, Institut Fédératif de Recherche 50, Nice, France.
authors: S
authors: S
authors: Sacconi
authors: D
authors: D
authors: Simkin
authors: N
authors: N
authors: Arrighi
authors: F
authors: F
authors: Chapon
authors: M M
authors: MM
authors: Larroque
authors: S
authors: S
authors: Vicart
authors: D
authors: D
authors: Sternberg
authors: B
authors: B
authors: Fontaine
authors: J
authors: J
authors: Barhanin
authors: C
authors: C
authors: Desnuelle
authors: S
authors: S
authors: Bendahhou
mesh_terms: D000328:Adult; D000368:Aged; D050030:Andersen Syndrome / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D002478:Cells, Cultured; D006801:Humans; D017136:Ion Transport; D008297:Male; D008564:Membrane Potentials; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D018482:Muscle, Skeletal / Q000473:pathology* / Q000503:physiopathology; D009154:Mutation; D032446:Myoblasts / Q000502:physiology; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000502:physiology
chemical_list: C489457:KCNJ2 protein, human; D024661:Potassium Channels, Inwardly Rectifying