Lateral transmission of force is impaired in skeletal muscles of dystrophic mice and very old rats
Lateral transmission of force is impaired in skeletal muscles of dystrophic mice and very old rats
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DOI：
10.1113/jphysiol.2010.201921
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发表时间：
2011-03-01
影响因子：
5.5
通讯作者：
Faulkner, John A.
中科院分区：
文献类型：
--
作者：
Ramaswamy, Krishnan S.;Palmer, Mark L.;Faulkner, John A.
非技术性概述青蛙肌肉中的单纤维产生的力被横向传递到肌肉表面，几乎没有或没有损失。为了在哺乳动物中证明这种现象，开发了一种“轭”装置，该装置附着在整个平行肌肉的表面上，并允许测量力的横向传递。然后，我们证明，对于野生型小鼠和大鼠，肌肉中的力的纵向和横向传递没有不同。相反，对于营养不良的小鼠和非常老的大鼠的骨骼肌，其中肌营养不良蛋白相关的糖蛋白复合物（DGC）的纤维被破坏，横向传递的力严重受损。我们的结论是，在骨骼肌收缩过程中，一个完整的DGC是必不可少的侧向力的传递和中断的DGC导致肌节不稳定和收缩诱导的损伤dystrophin-glycoprotein complex（DGC）提供了一个必不可少的联系，从肌纤维细胞骨架的细胞外基质。在营养不良的人类和mdx小鼠中，肌营养不良蛋白基因的突变破坏了DGC的结构，导致肌肉纤维严重受损。在青蛙肌肉中，从激活的纤维到肌肉表面的力的横向传递没有衰减，但在哺乳动物肌肉中还没有证明力的横向传递。一种独特的“轭”装置被开发出来，附着在肌腱中间的肌肉外膜上，能够测量侧向力。我们现在报告说，在年轻的野生型（WT）小鼠和大鼠的肌肉，在很宽的范围内的纵向力相比，横向传输的力量显示很少或没有减少。相比之下，mdx小鼠和老年大鼠的肌肉，横向传递的力量严重受损。mdx小鼠和老年大鼠的肌肉中肌营养不良蛋白的表达都有明显的减少。我们的结论是，在收缩过程中，由年轻的WT小鼠和大鼠的骨骼肌开发的力量是横向传输的纤维到纤维通过DGC没有减量。相比之下，在营养不良或非常老的动物的肌肉中，DGC结构和功能的中断损害力的横向传递，导致不稳定性和纤维对收缩诱导的损伤的敏感性增加。
Non-technical summaryThe force developed by a single fibre in frog muscles is transmitted laterally to the muscle surface with little or no loss. To demonstrate this phenomenon in mammals, a 'yoke' apparatus was developed that attached to the surface of whole, parallel-fibred muscles and permitted measurements of the lateral transmission of forces. We then demonstrated that for wild-type mice and rats longitudinal and lateral transmission of forces in muscles were not different. In contrast, for skeletal muscles of dystrophic mice and very old rats, in which the dystrophin-associated glycoprotein complex (DGC) of fibres was disrupted, the forces transmitted laterally were impaired severely. We conclude that during contractions of skeletal muscles, an intact DGC is essential for the lateral transmission of force and disruptions of the DGC lead to sarcomere instability and contraction-induced injury.The dystrophin-glycoprotein complex (DGC) provides an essential link from the muscle fibre cytoskeleton to the extracellular matrix. In dystrophic humans and mdx mice, mutations in the dystrophin gene disrupt the structure of the DGC causing severe damage to muscle fibres. In frog muscles, transmission of force laterally from an activated fibre to the muscle surface occurs without attenuation, but lateral transmission of force has not been demonstrated in mammalian muscles. A unique 'yoke' apparatus was developed that attached to the epimysium of muscles midway between the tendons and enabled the measurement of lateral force. We now report that in muscles of young wild-type (WT) mice and rats, compared over a wide range of longitudinal forces, forces transmitted laterally showed little or no decrement. In contrast, for muscles of mdx mice and very old rats, forces transmitted laterally were impaired severely. Muscles of both mdx mice and very old rats showed major reductions in the expression of dystrophin. We conclude that during contractions, forces developed by skeletal muscles of young WT mice and rats are transmitted laterally from fibre to fibre through the DGC without decrement. In contrast, in muscles of dystrophic or very old animals, disruptions in DGC structure and function impair lateral transmission of force causing instability and increased susceptibility of fibres to contraction-induced injury.