Impaired Ca2+ store functions in skeletal and cardiac muscle cells from sarcalumenin-deficient mice.
Sarcalumenin (SAR), specifically expressed in striated muscle cells, is a Ca2+-binding protein localized in the sarcoplasmic reticulum (SR) of the intracellular Ca2+ store. By generating SAR-deficient mice, we herein examined its physiological role. The mutant mice were apparently normal in growth, health, and reproduction, indicating that SAR is not essential for fundamental muscle functions. SAR-deficient skeletal muscle carrying irregular SR ultrastructures retained normal force generation but showed slow relaxation phases after contractions. A weakened Ca2+ uptake activity was detected in the SR prepared from mutant muscle, indicating that SAR contributes to Ca2+ buffering in the SR lumen and also to the maintenance of Ca2+ pump proteins. Cardiac myocytes from SAR-deficient mice showed slow contraction and relaxation accompanied by impaired Ca2+ transients, and the mutant mice exhibited a number of impairments in cardiac performance as determined in electrocardiography, ventricular catheterization, and echocardiography. The results obtained demonstrate that SAR plays important roles in improving the Ca2+ handling functions of the SR in striated muscle.
Yoshida
Morikatsu
M
Medical Chemistry and Molecular Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan.
Minamisawa
Susumu
S
Shimura
Miei
M
Komazaki
Shinji
S
Kume
Hideaki
H
Zhang
Miao
M
Matsumura
Kiyoyuki
K
Nishi
Miyuki
M
Saito
Minori
M
Saeki
Yasutake
Y
Ishikawa
Yoshihiro
Y
Yanagisawa
Teruyuki
T
Takeshima
Hiroshi
H
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D051381:Rats
D008565:Membrane Proteins; C070323:sarcalumenin; D002118:Calcium