Increase of skeletal muscle relaxation speed by direct injection of parvalbumin cDNA.

Increase of skeletal muscle relaxation speed by direct injection of parvalbumin cDNA.
复制标题

通过直接注射小清蛋白 cDNA 增加骨骼肌松弛速度。

DOI:
--
复制
发表时间:
1995
影响因子:
11.1
通讯作者:
Martin W. Berchtold
Martin W. Berchtold
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Markus Müntener;Lorenzo Käser;Jacqueline Weber;Martin W. Berchtold

文献摘要

被引文献

相似文献

小清蛋白(Parvalbumin,PV)是一种高浓度的钙离子结合蛋白,存在于脊椎动物骨骼肌纤维中,具有快速收缩/舒张功能。已经提出PV通过促进Ca 2+从肌原纤维向肌浆网的转运而在肌肉松弛过程中起作用。然而,在体外PV的金属结合动力学的基础上,这一假设受到了挑战。为了研究PV在骨骼肌纤维中的功能,将直接基因转移应用于正常和再生的大鼠比目鱼肌中,这些肌肉不合成可检测量的PV。在体内转染PV cDNA后两周,在正常肌肉中检测到相当水平的PV mRNA和蛋白,并且在再生肌肉中检测到更高的量。在转染的肌肉中,抽搐半松弛时间以剂量依赖性方式显著缩短,而收缩时间保持不变。观察到的半弛豫时间缩短是由于PV及其结合Ca 2+的能力,因为缺乏Ca(2+)结合能力的突变蛋白质不会促进生理学的任何变化。这些结果直接证明了PV作为哺乳动物骨骼肌松弛因子的生理功能。
Parvalbumin (PV) is a high affinity Ca(2+)-binding protein found at high concentration in fast-contracting/relaxing skeletal muscle fibers of vertebrates. It has been proposed that PV acts in the process of muscle relaxation by facilitating Ca2+ transport from the myofibrils to the sarcoplasmic reticulum. However, on the basis of metal-binding kinetics of PV in vitro, this hypothesis has been challenged. To investigate the function of PV in skeletal muscle fibers, direct gene transfer was applied in normal and regenerating rat soleus muscles which do not synthesize detectable amounts of PV. Two weeks after in vivo transfection with PV cDNA, considerable levels of PV mRNA and protein were detected in normal muscle, and even higher amounts were detected in regenerating muscle. Twitch half-relaxation time was significantly shortened in a dose-dependent way in transfected muscles, while contraction time remained unaltered. The observed shortening of half-relaxation time is due to PV and its ability to bind Ca2+, because a mutant protein lacking Ca(2+)-binding capacity did not promote any change in physiology. These results directly demonstrate the physiological function of PV as a relaxing factor in mammalian skeletal muscle.