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1 Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, USA; Center on Aging, University of Minnesota, Minneapolis, MN, USA
2 Department of Physical Therapy, Georgia State University, Atlanta, GA, USA
3 Center on Aging, University of Minnesota, Minneapolis, MN, USA; School of Kinesiology, University of Minnesota, Minneapolis, MN, USA
4 Center on Aging, University of Minnesota, Minneapolis, MN, USA; Department of Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis, MN, USA
* To whom correspondence should be addressed. E-mail: dl{at}ddt.biochem.umn.edu.
The study's purpose 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 wk 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. Four and 8-10 wk of increased muscle activity in rats aged ~32 mo 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). Two and 4 wk of decreased muscle activity 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.
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