Upregulation of store-operated Ca2+ entry in dystrophic mdx mouse muscle.
Store-operated Ca(2+) entry (SOCE) is an important mechanism in virtually all cells. In adult skeletal muscle, this mechanism is highly specialized for the rapid delivery of Ca(2+) from the transverse tubule into the junctional cleft during periods of depleting Ca(2+) release. In dystrophic muscle fibers, SOCE may be a source of Ca(2+) overload, leading to cell necrosis. However, this possibility is yet to be examined in an adult fiber during Ca(2+) release. To examine this, Ca(2+) in the tubular system and cytoplasm were simultaneously imaged during direct release of Ca(2+) from sarcoplasmic reticulum (SR) in skeletal muscle fibers from healthy (wild-type, WT) and dystrophic mdx mouse. The mdx fibers were found to have normal activation and deactivation properties of SOCE. However, a depression of the cytoplasmic Ca(2+) transient in mdx compared with WT fibers was observed, as was a shift in the SOCE activation and deactivation thresholds to higher SR Ca(2+) concentrations ([Ca(2+)](SR)). The shift in SOCE activation and deactivation thresholds was accompanied by an approximately threefold increase in STIM1 and Orai1 proteins in dystrophic muscle. While the mdx fibers can introduce more Ca(2+) into the fiber for an equivalent depletion of [Ca(2+)](SR) via SOCE, it remains unclear whether this is deleterious.
Edwards
Joshua N
JN
School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia.
Friedrich
Oliver
O
Cully
Tanya R
TR
von Wegner
Frederic
F
Murphy
Robyn M
RM
Launikonis
Bradley S
BS
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling; D003593:Cytoplasm / Q000378:metabolism; D004195:Disease Models, Animal; D056966:Excitation Contraction Coupling; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D018101:Mice, Inbred mdx; D018613:Microscopy, Confocal; D018482:Muscle, Skeletal / Q000378:metabolism*; D009136:Muscular Dystrophies / Q000235:genetics / Q000378:metabolism*; D000071740:ORAI1 Protein; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D000071737:Stromal Interaction Molecule 1
D015220:Calcium Channels; D008562:Membrane Glycoproteins; D000071740:ORAI1 Protein; C520430:Orai1 protein, mouse; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1