Increased hypertrophic response with increased mechanical load in skeletal muscles receiving identical activity patterns

It is often assumed that mechanical factors are important for effects of exercise on muscle, but during voluntary training and most experimental conditions the effects could solely be attributed to differences in electrical activity, and direct evidence for a mechanosensory pathway has been scarce. We here show that, in rat muscles stimulated in vivo under deep anesthesia with identical electrical activity patterns, isometric contractions induced twofold more hypertrophy than contractions with 50-60% of the isometric force. The number of myonuclei and the RNA levels of myogenin and myogenic regulatory factor 4 were increased with high load, suggesting that activation of satellite cells is mechano dependent. On the other hand, training induced a major shift in fiber type distribution from type 2b to 2x that was load independent, indicating that the electrical signaling rather than mechanosignaling controls fiber type. RAC-alpha serine/threonine-protein kinase (Akt) and ribosomal protein S6 kinase beta-1 (S6K1) were not significantly differentially activated by load, suggesting that the differences in mechanical factors were not important for activating the Akt/mammalian target of rapamycin/S6K1 pathway. The transmembrane molecule syndecan-4 implied in overload hypertrophy in cardiac muscle was not load dependent, suggesting that mechanosignaling in skeletal muscle is different.