Depressed contractile performance and reduced fatigue resistance in single skinned fibers of soleus muscle after long-term disuse in rats

Abstract

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.

The Effects of Dokhwalgisaeng-tang against Disuse Muscle Atrophy in Gastrocnemius of Rats

“…3) [26]. Udaka et al reported that the decrease in muscle weight due to muscle non-use is accompanied by a decrease in muscle fiber [27]. In this study, a decrease in the size of muscle fibers accompanied by a decrease in gastrocnemius muscle weight was observed following ankle fixation for 2 weeks.…”

Plasticity in central neural drive with short-term disuse and recovery - effects on muscle strength and influence of aging

“…possibly due to a loss of thick and thin myofilaments (Hvid et al 2017;Udaka et al 2011) potentially resulting in an altered force-length relationship (i.e. reduced overlap between actin and myosin at longer vs shorter muscle lengths).…”

The Protective Effects of Zanthoxylum bungeanum Maxim Pharmacopuncture on Disuse Muscle Atrophy in Rat Gastrocnemius Muscle

“…Disuse muscle atrophy can be induced experimentally through bandaging [26], receiving a nerve block [27], or having the tail suspended [28]. The nerve block method is useful for studying the pathology of surgical injuries where nerve function is altered.…”

“…Tail hanging is an appropriate and effective method used in the absence of weight loading, whilst maintaining skeletal mass and weightless atrophy. Bandage fixation, where artificial immobilization of the limb occurs, is the most widely used method in the study of muscular atrophy [26]. In this study, casting tape was used to fix the limb and induce disuse muscle atrophy.…”

“…2). Udaka et al [26] reported that the decrease in muscle weight due to the lack of use of muscle was accompanied by a decrease in muscle fiber in the muscle. In this current study, the decrease in muscle fiber size was observed along with a decrease in muscle weight due to ankle fixation for 2 weeks.…”