title: 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.
authors: Department of Cell Physiology, The Jikei University School of Medicine, Tokyo, Japan.
authors: Jun
authors: J
authors: Udaka
authors: Takako
authors: T
authors: Terui
authors: Iwao
authors: I
authors: Ohtsuki
authors: Keishi
authors: K
authors: Marumo
authors: Shin'ichi
authors: S
authors: Ishiwata
authors: Satoshi
authors: S
authors: Kurihara
authors: Norio
authors: N
authors: Fukuda
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D005221:Fatigue / Q000378:metabolism / Q000503:physiopathology*; D019417:Hindlimb Suspension / Q000379:methods; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D020966:Muscular Disorders, Atrophic / Q000378:metabolism / Q000503:physiopathology*; D009210:Myofibrils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D009997:Osmotic Pressure / Q000187:drug effects / Q000502:physiology; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012503:Saponins / Q000494:pharmacology; D012518:Sarcomeres / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D014336:Troponin / Q000378:metabolism
chemical_list: D010710:Phosphates; D012503:Saponins; D014336:Troponin; D002110:Caffeine; D018995:Myosin Heavy Chains; D002118:Calcium