Gadolinium reduces short-term stretch-induced muscle damage in isolated mdx mouse muscle fibres
Gadolinium reduces short-term stretch-induced muscle damage in isolated mdx mouse muscle fibres
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DOI：
10.1113/jphysiol.2003.047373
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发表时间：
2003-10-15
影响因子：
5.5
通讯作者：
Allen, DG
中科院分区：
文献类型：
--
作者：
Yeung, EW;Head, SI;Allen, DG
杜氏肌营养不良症是一种致命的肌肉疾病，由蛋白质肌营养不良蛋白的缺乏引起的，该蛋白质肌营养不良蛋白是位于表面膜的细胞内表面上的糖蛋白复合物的一部分。肌营养不良蛋白的确切功能以及其缺失导致严重肌肉损伤的原因尚不清楚。拉伸引起的肌肉损伤在正常肌肉中得到了很好的识别，并且在缺乏肌营养不良蛋白的动物（mdx小鼠）的肌肉中更为严重。已经提出牵张诱导的损伤是肌营养不良症损伤进展的基础。在本研究中，我们证实，来自mdx肌肉的单纤维更容易受到牵张诱导的损伤，并表明细胞内钠浓度（[Na+]（i））的相关升高大于野生型小鼠。我们发现，[Na+]（i）的这种上升可以被Gd 3+阻止，Gd 3+是一种已建立的牵张激活通道阻滞剂。mdx纤维具有高于正常静息的[Na+]（i），并且这也被Gd 3+降低。如果在[Na+]（i）随拉伸收缩而升高的时间内施加Gd 3+，它会阻止减少的力的一个分量。另一个减少的力是由肌节的不均匀性引起的，可以通过将肌肉拉伸到新的最佳长度来最小化。这些实验表明，部分由mdx纤维拉伸引起的短期损伤可以通过阻断拉伸激活通道来预防。
Duchenne muscular dystrophy is a lethal muscle disease caused by absence of the protein dystrophin which is part of a glycoprotein complex located on the intracellular surface of the surface membrane. The precise function of dystrophin and the reason why its absence causes severe muscle damage are unclear. Stretch-induced muscle damage is well recognised in normal muscle and is more severe in muscles from animals lacking dystrophin (mdx mice). It has been proposed that stretch-induced damage underlies the progression of damage in muscular dystrophy. In the present study we confirm that single fibres from mdx muscle are more susceptible to stretch-induced damage and show that there is an associated rise in intracellular sodium concentration ([Na+](i)) which is greater than in wild-type mice. We show that this rise in [Na+](i) can be prevented by Gd3+, which is an established blocker of stretch-activated channels. mdx fibres have a higher than normal resting [Na+](i) and this is also reduced by Gd3+. If Gd3+ is applied over the period in which [Na+](i) rises following stretched contraction, it prevents one component of the reduced force. The other component of reduced force is caused by inhomogeneity of sarcomeres and can be minimised by stretching the muscle to its new optimum length. These experiments show that part of the short-term damage caused by stretch in mdx fibres can be prevented by blocking stretch-activated channels.