Department of Cell Physiology, The Jikei University School of Medicine, Tokyo, Japan.
J Appl Physiol (1985). 2011 Oct;111(4):1080-7. doi: 10.1152/japplphysiol.00330.2011. Epub 2011 Jun 30.
Long-term disuse results in atrophy in skeletal muscle, which is characterized by reduced functional capability, impaired locomotor condition, and reduced resistance to fatigue. Here we show how long-term disuse affects contractility and fatigue resistance in single fibers of soleus muscle taken from the hindlimb immobilization model of the rat. We found that long-term disuse results in depression of caffeine-induced transient contractions in saponin-treated single fibers. However, when normalized to maximal Ca(2+)-activated force, the magnitude of the transient contractions became similar to that in control fibers. Control experiments indicated that the active force depression in disused muscle is not coupled with isoform switching of myosin heavy chain or troponin, or with disruptions of sarcomere structure or excessive internal sarcomere shortening during contraction. In contrast, our electronmicroscopic observation supported our earlier observation that interfilament lattice spacing is expanded after disuse. Then, to investigate the molecular mechanism of the reduced fatigue resistance in disused muscle, we compared the inhibitory effects of inorganic phosphate (Pi) on maximal Ca(2+)-activated force in control vs. disused fibers. The effect of Pi was more pronounced in disused fibers, and it approached that observed in control fibers after osmotic compression. These results suggest that contractile depression in disuse results from the lowering of myofibrillar force-generating capacity, rather than from defective Ca(2+) mobilization, and the reduced resistance to fatigue is from an enhanced inhibitory effect of Pi coupled with a decrease in the number of attached cross bridges, presumably due to lattice spacing expansion.
长期不活动会导致骨骼肌萎缩，其特征是功能能力降低、运动能力受损和抗疲劳能力降低。在这里，我们展示了长期不活动如何影响来自大鼠后肢固定模型的比目鱼肌单纤维的收缩性和抗疲劳性。我们发现，长期不活动导致皂素处理的单纤维中咖啡因诱导的短暂收缩性降低。然而，当归一化到最大 Ca(2+)-激活力时，短暂收缩的幅度变得与对照纤维相似。对照实验表明，不活动肌肉中的主动力降低与肌球蛋白重链或肌钙蛋白的同工型转换、肌节结构的破坏或收缩期间过度的内部肌节缩短无关。相比之下，我们的电子显微镜观察结果支持了我们之前的观察结果，即不活动后，原纤维晶格间距扩大。然后，为了研究不活动肌肉中抗疲劳性降低的分子机制，我们比较了无机磷酸盐 (Pi) 在对照和不活动纤维中对最大 Ca(2+)-激活力的抑制作用。Pi 的作用在不活动纤维中更为明显，并且在渗透压压缩后接近对照纤维中观察到的作用。这些结果表明，不活动引起的收缩性降低是由于肌原纤维产生力的能力降低，而不是由于 Ca(2+) 动员缺陷所致，抗疲劳性降低是由于 Pi 的抑制作用增强，以及附着的横桥数量减少所致，可能是由于晶格间距扩大所致。
