Stretch activation combats force loss from fatigue in fast-contracting mouse skeletal muscle fibers

Stretch activation (SA) is the delayed increase in force following a rapid stretch and improves muscle performance during repetitive cyclical contractions in insect flight and cardiac muscles. Although historically considered too low to be physiologically relevant in skeletal muscle, our recent work showed that higher phosphate concentrations ([P_i]) increased SA in mouse soleus fibers. These results suggest SA has a role combating fatigue, which increases [P_i], lowers pH, and reduces active calcium concentration ([Ca²⁺]). To test this, we measured SA during Active, High [Ca²⁺] Fatigue and Low [Ca²⁺] Fatigue conditions in myosin heavy chain (MHC) I, IIA, IIX, and IIB fibers from mouse soleus and extensor digitorum longus muscles. In the fast-contracting MHC II fibers, calcium-activated isometric tension (F₀) decreased from Active to High [Ca²⁺] Fatigue to Low [Ca²⁺] Fatigue, as expected. Remarkably, SA tension (F_SA) was not decreased but remained unchanged or increased under High and Low [Ca²⁺] Fatigue, except for a small decrease in MHC IIB fibers in Low [Ca²⁺] Fatigue compared with Active. This results in SA’s percent contribution to total tension production (F_SA/[F₀ + F_SA]) being much greater (58–114%) under fatiguing conditions in fast-contracting MHC II fibers. The SA tension peak for MHC I fibers was not visibly apparent under either fatigue condition, and the peak was about 20% of MHC II fibers’ peaks under active conditions. Our results show SA improves force production under fatiguing conditions in MHC II fibers, which could play an important role in increasing endurance for muscles that are lengthened prior to shortening.