Compromised store-operated Ca2+ entry in aged skeletal muscle.
In aged skeletal muscle, changes to the composition and function of the contractile machinery cannot fully explain the observed decrease in the specific force produced by the contractile machinery that characterizes muscle weakness during aging. Since modification in extracellular Ca(2+) entry in aged nonexcitable and excitable cells has been recently identified, we evaluated the functional status of store-operated Ca(2+) entry (SOCE) in aged mouse skeletal muscle. Using Mn(2+) quenching of Fura-2 fluorescence and confocal-microscopic imaging of Ca(2+) movement from the transverse tubules, we determined that SOCE was severely compromised in muscle fibers isolated from aged mice (26-27 months) as compared with those from young (2-5 months) mice. While reduced SOCE in aged skeletal muscle does not appear to result from altered expression levels of STIM1 or reduced expression of mRNA for Orai, this reduction in SOCE is mirrored in fibers isolated from young mice null for mitsugumin-29, a synaptophysin-related protein that displays decreased expression in aged skeletal muscle. Our data suggest that decreased mitsugumin-29 expression and reduced SOCE may contribute to the diminished intracellular Ca(2+) homeostatic capacity generally associated with muscle aging.
Zhao
Xiaoli
X
Department of Physiology and Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Weisleder
Noah
N
Thornton
Angela
A
Oppong
Yaa
Y
Campbell
Rachel
R
Ma
Jianjie
J
Brotto
Marco
M
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D002460:Cell Line; D008297:Male; D008345:Manganese / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D009124:Muscle Proteins / Q000172:deficiency; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D000071740:ORAI1 Protein; D015203:Reproducibility of Results; D000071737:Stromal Interaction Molecule 1; D016708:Synaptophysin / Q000172:deficiency
D015220:Calcium Channels; D008562:Membrane Glycoproteins; C111842:Mg29 protein, mouse; D009124:Muscle Proteins; D000071740:ORAI1 Protein; C520430:Orai1 protein, mouse; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; D016708:Synaptophysin; D008345:Manganese; D002118:Calcium