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Orai1-dependent calcium entry promotes skeletal muscle growth and limits fatigue

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Listed:
  • Lan Wei-LaPierre

    (University of Rochester)

  • Ellie M. Carrell

    (University of Rochester)

  • Simona Boncompagni

    (University G. d’Annunzio)

  • Feliciano Protasi

    (University G. d’Annunzio)

  • Robert T. Dirksen

    (University of Rochester)

Abstract

Store-operated Ca2+ entry (SOCE) in skeletal muscle involves signalling between stromal-interacting molecule 1 (STIM1) in the sarcoplasmic reticulum (SR) and Ca2+ selective Orai1 channels in the sarcolemma. Here we generate transgenic mice with muscle-specific expression of dominant-negative Orai1 (dnOrai1) and demonstrate that Orai1-dependent SOCE promotes growth and limits fatigue in adult skeletal muscle. dnOrai1 mice lack SOCE specifically in muscle but are fertile and thrive well into adulthood. Although muscle ultrastructure, excitation–contraction (EC) coupling, fibre type, and expression of other Ca2+ regulatory proteins are unaltered, dnOrai1 mice exhibit reduced body weight, muscle mass and fibre cross-sectional area. Importantly, during intense repetitive activity, dnOrai1 mice display increased susceptibility to fatigue at the single fibre, excised muscle and whole-animal levels. We further show that STIM1 and Orai1 proteins co-localize within the triad junction but do not exist in a preassembled context. These results show that Orai1-dependent SOCE has an important physiological role in muscles of adult mice.

Suggested Citation

  • Lan Wei-LaPierre & Ellie M. Carrell & Simona Boncompagni & Feliciano Protasi & Robert T. Dirksen, 2013. "Orai1-dependent calcium entry promotes skeletal muscle growth and limits fatigue," Nature Communications, Nature, vol. 4(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3805
    DOI: 10.1038/ncomms3805
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