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 Minen 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 electrocardiograpliy, 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.