Impaired Ca2+ store functions in skeletal and cardiac muscle cells from sarcalumenin-deficient mice
Impaired Ca2+ store functions in skeletal and cardiac muscle cells from sarcalumenin-deficient mice
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DOI：
10.1074/jbc.m406618200
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发表时间：
2005-02-04
影响因子：
4.8
通讯作者：
Takeshima, H
中科院分区：
文献类型：
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作者：
Yoshida, M;Minamisawa, S;Takeshima, H
Sarealumenin（SAR）是一种特异性表达于横纹肌细胞的钙结合蛋白，定位于肌浆网（SR）的细胞内钙库。通过产生SAR缺陷小鼠，我们在此研究了其生理作用。突变小鼠在生长、健康和繁殖方面明显正常，表明SAR对基本肌肉功能不是必需的。SAR缺陷的骨骼肌进行不规则SR超微结构保留正常的力产生，但收缩后表现出缓慢的松弛阶段。在从突变体肌肉制备的SR中检测到减弱的Ca 2（+）摄取活性，表明SAR有助于SR腔中的Ca 2+缓冲以及Ca 2+泵蛋白的维持。SAR缺陷小鼠的心肌细胞表现出缓慢的收缩和舒张，伴随着受损的Ca 2+瞬变，和突变小鼠表现出一些损害的心脏功能，在心电图，心室导管插入术，和超声心动图。结果表明，SAR在改善横纹肌SR的Ca ~（2+）处理功能中起重要作用。
Sarealumenin (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.