| First Author | Wei-Lapierre L | Year | 2013 |
| Journal | Nat Commun | Volume | 4 |
| Pages | 2805 | PubMed ID | 24241282 |
| Mgi Jnum | J:212576 | Mgi Id | MGI:5581785 |
| Doi | 10.1038/ncomms3805 | Citation | Wei-Lapierre L, et al. (2013) Orai1-dependent calcium entry promotes skeletal muscle growth and limits fatigue. Nat Commun 4:2805 |
| abstractText | Store-operated Ca(2)(+) entry (SOCE) in skeletal muscle involves signalling between stromal-interacting molecule 1 (STIM1) in the sarcoplasmic reticulum (SR) and Ca(2)(+) 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 Ca(2)(+) 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. |
