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 M, Minamisawa S, Shimura M, Komazaki S, Kume H, Zhang M, Matsumura K, Nishi M, Saito M, Saeki Y, Ishikawa Y, Yanagisawa T, Takeshima H. Impaired Ca2+ store functions in skeletal and cardiac muscle cells from sarcalumenin-deficient mice. Journal of Biological Chemistry. 2005 Feb 4;280(5):3500-6. doi: 10.1074/jbc.M406618200
American Society for Biochemistry and Molecular Biology