Mechanisms underlying Andersen's syndrome pathology in skeletal muscle are revealed in human myotubes

S. Sacconi, D. Simkin, N. Arrighi, F. Chapon, M. M. Larroque, S. Vicart, D. Sternberg, B. Fontaine, J. Barhanin, C. Desnuelle, S. Bendahhou*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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 α-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 Ba 2+-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.

Original languageEnglish (US)
Pages (from-to)C876-C885
JournalAmerican Journal of Physiology - Cell Physiology
Volume297
Issue number4
DOIs
StatePublished - 2009
Externally publishedYes

Keywords

  • Andersen's syndrome
  • Potassium ion channels
  • Skeletal muscle

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Mechanisms underlying Andersen's syndrome pathology in skeletal muscle are revealed in human myotubes'. Together they form a unique fingerprint.

Cite this