Connor E A, Qin K, Yankelev H, DeStefano D
Department of Biology, University of Massachusetts, Amherst 01003.
J Cell Biol. 1994 Dec;127(5):1435-45. doi: 10.1083/jcb.127.5.1435.
Denervation of skeletal muscle results in dramatic remodeling of the cellular and molecular composition of the muscle connective tissue. This remodeling is concentrated in muscle near neuromuscular junctions and involves the accumulation of interstitial cells and several extracellular matrix molecules. Given the role of extracellular matrix in neurite outgrowth and synaptogenesis, we predict that this remodeling of the junctional connective tissue directly influences the regeneration of the neuromuscular junction. As one step toward understanding the role of this denervation-induced remodeling in synapse formation, we have begun to look for the signals that are involved in initiating the junctional accumulations of interstitial cells and matrix molecules. Here, the role of muscle inactivity as a signal was examined. The distributions of interstitial cells, fibronectin, and tenascin were determined in muscles inactivated by presynaptic blockade of muscle activity with tetrodotoxin. We found that blockade of muscle activity for up to 4 wk produced neither the junctional accumulation of interstitial cells nor the junctional concentrations of tenascin and fibronectin normally present in denervated frog muscle. In contrast, the muscle inactivity induced the extrajunctional appearance of two synapse-specific molecules, the acetylcholine receptor and a muscle fiber antigen, mAb 3B6. These results demonstrate that the remodeling of the junctional connective tissue in response to nerve injury is a unique response of muscle to denervation in that it is initiated by a mechanism that is independent of muscle activity. Thus connective tissue remodeling in denervated skeletal muscle may be induced by signals released from or associated with the nerve other than the evoked release of neurotransmitter.
骨骼肌去神经支配会导致肌肉结缔组织的细胞和分子组成发生显著重塑。这种重塑集中在神经肌肉接头附近的肌肉中，涉及间质细胞和几种细胞外基质分子的积累。鉴于细胞外基质在神经突生长和突触形成中的作用，我们预测这种接头结缔组织的重塑直接影响神经肌肉接头的再生。作为理解这种去神经支配诱导的重塑在突触形成中作用的第一步，我们开始寻找参与启动间质细胞和基质分子接头积累的信号。在此，研究了肌肉不活动作为一种信号的作用。用河豚毒素对肌肉活动进行突触前阻断使肌肉失活，然后测定间质细胞、纤连蛋白和腱生蛋白的分布。我们发现，长达4周的肌肉活动阻断既未产生间质细胞的接头积累，也未产生去神经支配的青蛙肌肉中通常存在的腱生蛋白和纤连蛋白的接头浓度。相反，肌肉不活动诱导了两种突触特异性分子——乙酰胆碱受体和一种肌肉纤维抗原mAb 3B6在接头外出现。这些结果表明，神经损伤后接头结缔组织的重塑是肌肉对去神经支配的一种独特反应，因为它是由一种独立于肌肉活动的机制启动的。因此，去神经支配的骨骼肌中的结缔组织重塑可能是由从神经释放或与神经相关的信号诱导的，而不是由神经递质的诱发释放诱导的。
