Andersen’s syndrome mutants produce a knockdown of inwardly rectifying K + channel in mouse skeletal muscle in vivo

Dina Simkin, Gaëlle Robin, Serena Giuliano, Ana Vukolic, Pamela Moceri, Nicolas Guy, Kay Dietrich Wagner, Alain Lacampagne, Bruno Allard, Saïd Bendahhou*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Andersen’s syndrome (AS) is a rare autosomal disorder that has been defined by the triad of periodic paralysis, cardiac arrhythmia, and developmental anomalies. AS has been directly linked to over 40 different autosomal dominant negative loss-of-function mutations in the KCNJ2 gene, encoding for the tetrameric strong inward rectifying K + channel K IR 2.1. While K IR 2.1 channels have been suggested to contribute to setting the resting membrane potential (RMP) and to control the duration of the action potential (AP) in skeletal and cardiac muscle, the mechanism by which AS mutations produce such complex pathophysiological symptoms is poorly understood. Thus, we use an adenoviral transduction strategy to study in vivo subcellular distribution of wild-type (WT) and AS-associated mutant K IR 2.1 channels in mouse skeletal muscle. We determined that WT and D71V AS mutant K IR 2.1 channels are localized to the sarcolemma and the transverse tubules (T-tubules) of skeletal muscle fibers, while the ∆314-315 AS K IR 2.1 mutation prevents proper trafficking of the homo- or hetero-meric channel complexes. Whole-cell voltage-clamp recordings in individual skeletal muscle fibers confirmed the reduction of inwardly rectifying K + current (I K1 ) after transduction with ∆314-315 K IR 2.1 as compared to WT channels. Analysis of skeletal muscle function revealed reduced force generation during isometric contraction as well as reduced resistance to muscle fatigue in extensor digitorum longus muscles transduced with AS mutant K IR 2.1. Together, these results suggest that K IR 2.1 channels may be involved in the excitation–contraction coupling process required for proper skeletal muscle function. Our findings provide clues to mechanisms associated with periodic paralysis in AS.

Original languageEnglish (US)
Pages (from-to)309-323
Number of pages15
JournalCell and Tissue Research
Issue number2
StatePublished - Feb 1 2018


  • Adenovirus
  • Andersen’s syndrome
  • Channelopathies
  • K 2.1
  • Skeletal muscle

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology
  • Histology


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