title: Peripheral mechanisms of fatigue in muscles of normal and dystrophic mice.
abstract: We evaluated the contribution of different processes to fatigue of normal and dystrophic mouse muscles using an in vitro electromyography chamber. Fatigue was induced by repetitive nerve stimulation at 30 Hz for 0.5 s, every 2.5 s until tension decreased by about 50%. We monitored the compound nerve action potential (AP), compound muscle AP, and isometric tension responses to nerve stimulation, and compound muscle AP and tension responses to direct muscle stimulation. In normal mice, about 50% reduction in nerve-evoked tension occurred by 2.4 min in extensor digitorum longus (EDL), 4.8 min in diaphragm, and 9 min in soleus. Analysis of the responses revealed that the fatigue was caused by failure of more than one process in all muscles, and failure of nerve conduction did not contribute to fatigue in any muscle. Failure of neuromuscular transmission, muscle membrane excitation, and excitation-contraction (E-C) coupling and contractility accounted for 55, 45, and 0%, respectively, of the fatigue in EDL, for 21, 74, and 5% of the fatigue in diaphragm, and for 2, 54, and 44% of the fatigue in soleus. In dystrophic mice, while about 50% reduction in nerve-evoked tension occurred by 8.1 min in EDL and 5.6 min in diaphragm, only 29% reduction in tension occurred by 80 min in soleus. Failure of neuromuscular transmission, muscle membrane excitation, E-C coupling and contractility accounted for 22, 63 and 15% of the fatigue in EDL, for 21, 79, and 0% of the fatigue in diaphragm, and for 15, 59, and 26% of the fatigue in soleus. The proportion of slow-twitch oxidative fibers was more than normal in dystrophic EDL, but the same as normal in dystrophic diaphragm and soleus. The slower onset of fatigue was attributable to lesser failure of neuromuscular transmission in dystrophic EDL, and to lesser failure of E-C coupling and contractility in dystrophic soleus.
authors.affiliation: Department of Medicine, Maimonides Medical Center, Brooklyn, NY 11219.
authors.forename: M K
authors.initials: MK
authors.lastname: Pagala
authors.forename: S A
authors.initials: SA
authors.lastname: Venkatachari
authors.forename: N V
authors.initials: NV
authors.lastname: Nandakumar
authors.forename: K
authors.initials: K
authors.lastname: Ravindran
authors.forename: J
authors.initials: J
authors.lastname: Kerstein
authors.forename: T
authors.initials: T
authors.lastname: Namba
authors.forename: D
authors.initials: D
authors.lastname: Grob
mesh_terms: D000818:Animals; D003964:Diaphragm / Q000503:physiopathology; D004558:Electric Stimulation; D004576:Electromyography; D005221:Fatigue / Q000503:physiopathology*; D006651:Histocytochemistry; D051379:Mice; D008815:Mice, Inbred Strains; D009136:Muscular Dystrophies / Q000503:physiopathology*; D009469:Neuromuscular Junction / Q000502:physiology*; D012016:Reference Values