Growth‐related signaling increases with duty cycle following high force contractions in mouse tibialis anterior

Abstract

High force contractions (HFC) activate multiple cascades related to protein synthesis. Although some studies have suggested force‐dependent activation of various growth‐related kinases, we found no correlation between force magnitude and several members of these signaling cascades when metabolic stress was minimized. HFC impose both mechanical and metabolic stresses, and we hypothesized that MAPK phosphorylation during high force isometric activation would be increased when the work‐to‐rest ratio (duty cycle, DC) and metabolic cost are increased. Mouse tibialis anterior muscles were subjected to high (H, 15%) or low (L, 1.5%) DC stimulation protocols, using long or short duration activations to further manipulate ATP depletion. Force‐time integrals were ~4X greater in HDC than LDC and fatigue was evident in all groups except LDC, short activations. ACC phosphorylation, indicative of AMPK activity, was greater in HDC protocols indicating greater energetic stress. FAK and p38 phosphorylation were also greater in HDC than LDC, which could reflect either force or energy‐depletion dependent signaling. Akt phosphorylation decreased most in LDC with long activations, but ERK was similarly phosphorylated by stimulation in all groups. Combined with our previous observation of force‐independent signaling, we conclude that metabolic stress is a major contributor to high force‐related signaling. DC05017