Hyatt Jon-Philippe K, Roy Roland R, Baldwin Kenneth M, Edgerton V Reggie
Department of Physiological Science, University of California-Los Angeles, 621 Charles E. Young Drive, Los Angeles, CA 90095, USA.
Am J Physiol Cell Physiol. 2003 Nov;285(5):C1161-73. doi: 10.1152/ajpcell.00128.2003. Epub 2003 Jul 2.
Electrical activity is thought to be the primary neural stimulus regulating muscle mass, expression of myogenic regulatory factor genes, and cellular activity within skeletal muscle. However, the relative contribution of neural influences that are activity-dependent and -independent in modulating these characteristics is unclear. Comparisons of denervation (no neural influence) and spinal cord isolation (SI, neural influence with minimal activity) after 3, 14, and 28 days of treatment were used to demonstrate whether there are neural influences on muscle that are activity independent. Furthermore, the effects of these manipulations were compared for a fast ankle extensor (medial gastrocnemius) and a fast ankle flexor (tibialis anterior). The mass of both muscles plateaued at approximately 60% of control 2 wk after SI, whereas both muscles progressively atrophied to <25% of initial mass at this same time point after denervation. A rapid increase in myogenin and, to a lesser extent, MyoD mRNAs and proteins was observed in denervated and SI muscles: at the later time points, these myogenic regulatory factors remained elevated in denervated, but not in SI, muscles. This widespread neural activity-independent influence on MyoD and myogenin expression was observed in myonuclei and satellite cells and was not specific for fast or slow fiber phenotypes. Mitotic activity of satellite and connective tissue cells also was consistently lower in SI than in denervated muscles. These results demonstrate a neural effect independent of electrical activity that 1) helps preserve muscle mass, 2) regulates muscle-specific genes, and 3) potentially spares the satellite cell pool in inactive muscles.
电活动被认为是调节肌肉质量、肌源性调节因子基因表达以及骨骼肌细胞活性的主要神经刺激因素。然而，在调节这些特征方面，与活动相关和不相关的神经影响的相对贡献尚不清楚。通过比较治疗3天、14天和28天后去神经支配（无神经影响）和脊髓隔离（SI，最小活动量的神经影响）的情况，来证明是否存在与活动无关的对肌肉的神经影响。此外，还比较了这些操作对快速踝关节伸肌（腓肠肌内侧头）和快速踝关节屈肌（胫骨前肌）的影响。SI后2周，两块肌肉的质量均稳定在对照的约60%，而去神经支配后在同一时间点，两块肌肉均逐渐萎缩至初始质量的<25%。在去神经支配和SI的肌肉中观察到肌细胞生成素以及程度较轻的MyoD mRNA和蛋白质迅速增加：在后期时间点，这些肌源性调节因子在去神经支配的肌肉中仍然升高，但在SI的肌肉中则不然。在肌核和卫星细胞中观察到这种对MyoD和肌细胞生成素表达的广泛的与神经活动无关的影响，并且对快肌或慢肌纤维表型不具有特异性。SI中卫星细胞和结缔组织细胞的有丝分裂活性也始终低于去神经支配的肌肉。这些结果证明了一种与电活动无关的神经效应，即1）有助于维持肌肉质量，2）调节肌肉特异性基因，3）可能使不活动肌肉中的卫星细胞池得以保留。
