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Am J Physiol Regul Integr Comp Physiol 297: R900-R910, 2009. First published July 22, 2009; doi:10.1152/ajpregu.91043.2008
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ARTICLES

Causes of fatigue in slow-twitch rat skeletal muscle during dynamic activity

Morten Munkvik,1,2 Per Kristian Lunde,1,2 and Ole M. Sejersted1,2

1Institute for Experimental Medical Research, Oslo University Hospital, Ullevaal, Oslo, Norway; and 2Center for Heart Failure Research, University of Oslo, Oslo, Norway

Submitted 22 December 2008 ; accepted in final form 17 July 2009

Skeletal muscle fatigue is most often studied in vitro at room temperature and is classically defined as a decline in maximum force production or power output, exclusively linked to repeated isometric contractions. However, most muscles shorten during normal use, and we propose that both the functional correlate of fatigue, as well as the fatigue mechanism, will be different during dynamic contractions compared with static contractions. Under isoflurane anesthesia, fatigue was induced in rat soleus muscles in situ by isotonic shortening contractions at 37°C. Muscles were stimulated repeatedly for 1 s at 30 Hz every 2 s for a total of 15 min. The muscles were allowed to shorten isotonically against a load corresponding to one-third of maximal isometric force. Maximal unloaded shortening velocity (V0), maximum force production (Fmax), and isometric relaxation rate (–dF/dt) was reduced after 100 s but returned to almost initial values at the end of the stimulation protocol. Likewise, ATP and creatine phosphate (CrP) were reduced after 100 s, but the level of CrP was partially restored to initial values after 15 min. The rate of isometric force development, the velocity of shortening, and isotonic shortening were also reduced at 100 s, but in striking contrast, did not recover during the remainder of the stimulation protocol. The regulatory myosin light chain (MLC2s) was dephosphorylated after 100 s and did not recover. Although metabolic changes may account for the changes of Fmax, –dF/dt, and V0, dephosphorylation of MLC2s may be involved in the fatigue seen as sustained slower contraction velocities and decreased muscle shortening.

MLC phosphorylation; oxidative metabolism; isotonic contractions; work; aerobic exercise; cross-bridge



Address for reprint requests and other correspondence: M. Munkvik, Institute for Experimental Medical Research, Oslo Univ. Hospital, Ullevål, Kirkeveien 166, N-0407 Oslo, Norway (e-mail: morten.munkvik{at}medisin.uio.no)







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