Stretch activated force production increases during fatigue in fast-contracting skeletal muscle fibers.

Abstract

Stretch activation (FSA) is the delayed increase in fiber tension (force per cross-sectional area) following a rapid stretch and can improve muscle performance during repetitive cyclical contractions. Historically considered minimal in skeletal muscle, our recent work showed the ratio of stretch activation to calcium-activated tension (FSA/F0) increased from 10 to 40% with greater inorganic phosphate (Pi) levels in soleus muscle fibers (Straight et al., 2019). Given Pi increases with muscle fatigue, we hypothesize that FSA helps maintain force generation during fatigue. To test this, FSA, induced by a stretch of 0.5% fiber length, was examined during control (pCa 4.5, pH 7.0, Pi 5 mM), high calcium fatigue (pCa 4.5, pH 6.2, Pi 30 mM) and low calcium fatigue (pCa 5.1, pH 6.2, Pi 30 mM) in fibers expressing myosin heavy chain (MHC) I, IIA, IIX and IIB isoforms from soleus and extensor digitorum longus muscles of C57BL/6NJ mice. F0 of all MHC isoforms decreased from control to high calcium fatigue to low calcium fatigue, as expected. In MHC IIX and IIB fibers, FSA occurred under all conditions and FSA/F0 increased from control (17-20%) to high calcium fatigue (32-35%) to low calcium fatigue (42-44%). In MHC IIA fibers, FSA/F0 was similar to MHC IIX and IIB fibers in control and high calcium fatigue, however MHC I fiber values were much less (5% and 18%). For MHC I and IIA fibers, no discernable FSA was apparent in low calcium fatigue. These results show that FSA is a significant modulator of force production under fatiguing conditions in fast-contracting muscle fibers. This mechanism could play an important physiological role during cyclical contractions, when the antagonistic muscle rapidly stretches the agonist muscle, by reducing the effect of fatigue on force production.