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J Appl Physiol 96: 498-506, 2004. First published September 26, 2003; doi:10.1152/japplphysiol.00842.2003
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Muscle activity and aging affect myosin structural distribution and force generation in rat fibers

Dawn A. Lowe,1,2 Gordon L. Warren,5 LeAnn M. Snow,2,3 LaDora V. Thompson,2,4 and David D. Thomas1,2

1Department of Biochemistry, Molecular Biology, and Biophysics, 2Center on Aging, 3School of Kinesiology, and 4Department of Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis, Minnesota 55455; and 5Department of Physical Therapy, Georgia State University, Atlanta, Georgia 30303

Submitted 11 August 2003 ; accepted in final form 21 September 2003

The purpose of this study was to determine whether increased muscle activity could reverse myosin structural alterations that occur in aged rat muscle and whether those alterations could be induced in young rat muscle by decreased activity. Semimembranosus muscle activity was increased by electrical stimulation (200-ms trains, 154 Hz, 5 V) through a nerve cuff on the tibial branch of the ischiatic nerve. The protocol consisted of 5 sets of 6-10 maximal isometric contractions performed twice per week for 4 or 8-10 wk. Decreased muscle activity was induced by denervation of the semimembranosus muscle for 2 or 4 wk. Semimembranosus fibers were then studied for Ca2+-activated force generation. Fibers were also spin labeled on the myosin catalytic domain and studied using electron paramagnetic resonance (EPR) spectroscopy to assess myosin structural distribution. Increased muscle activity for 4 and 8-10 wk in ~32-mo-old rats resulted in -16 and +4% changes in specific tension, respectively (P < 0.01). EPR spectra showed that the fraction of myosin heads in the strong-binding structural state during contraction was reduced at 4 wk (0.241 ± 0.020 vs. 0.269 ± 0.018, P = 0.046) but returned to normal by 8-10 wk (P = 0.67). Decreased muscle activity for 2 and 4 wk in ~9-mo-old rats resulted in 23 and 34% reductions, respectively, in specific tension; EPR spectra showed 16 and 35% decreases in strong-binding myosin (P < 0.01). These data support the hypothesis that changes in muscle activity affect muscle strength, at least in part through alterations in myosin structure and function.

specific tension; permeabilized fiber; denervation; electron paramagnetic resonance spectroscopy



Address for reprint requests and other correspondence: D. A. Lowe, Univ. of Minnesota, BMBB Dept. 6-155 Jackson Hall, 321 Church St., Minneapolis, MN 55455 (E-mail: dl{at}ddt.biochem.umn.edu).




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