BPS2026 – Does stretch activation increase skeletal muscle endurance?

Stretch activation (SA) is the delayed increase in force following a rapid stretch and improves muscle performance during 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 (P i ) increased SA in mouse soleus fibers. These results suggest SA plays a role combating fatigue, which increases P i , lowers pH and reduces calcium concentration (Ca 2+ ). To test this, we measured SA during control, high Ca 2+ fatigue and low Ca 2+ fatigue conditions in myosin heavy chain (MHC) I, IIA, IIX, and IIB skinned fibers from mouse soleus and extensor digitorum longus muscles. In the fast-contracting MHC II fibers, calcium-activated isometric force (F 0 ) decreased from active to high Ca 2+ fatigue to low Ca 2+ fatigue, as expected. Remarkably, SA tension (F SA ) was not decreased but remained unchanged or increased under high and low Ca 2+ fatigue compared to control conditions. This results in SA’s percent contribution to total tension production (F SA /(F 0 +F SA )) being much greater (58%–114%) under fatiguing conditions in MHC II fibers. The SA tension peak for MHC I fibers was not apparent under either fatigue condition, and was about 20% of MHC II fibers’ peaks under control conditions. To account for the different fiber type responses to fatigue we propose two myosin-based mechanisms, the main difference being that for some myosin isoforms and conditions, stretch causes a reversal of the myosin power-stroke allowing for a subsequent “second” power-stroke, while in other cases, stretch forcibly detaches myosin from actin in a post-power stroke state. Our results show SA improves force production during fatigue in MHC type II fibers. This could play an important role in increasing endurance for muscles that are lengthened prior to shortening by supplementing calcium-activated force production.