Effects of contraction frequency during high-intensity training on fatigue resistance and aerobic adaptations in mouse skeletal muscle

In high-intensity and sprint interval training, the frequency of contractions is typically higher compared with moderate-intensity continuous training, but it remains unclear whether this contributes to the effective increase in fatigue resistance mechanisms. Here, we investigated the role of contraction frequency in high-intensity training on endurance adaptations of mouse skeletal muscle. Male C57BL/6 mice were divided into groups based on high (0.25 s contraction every 0.5 s) and low (0.25 s contraction every 4.5 s) contraction frequencies, with either 360 contractions per session (Hi360 and Lo360) or 30 contractions per session (Hi30 and Lo30). The plantar flexor muscles were stimulated using in vivo supramaximal electrical stimulation, where all muscle fibers were maximally activated, every other day for 5 wk. In both the Hi360 and Lo360 groups, where force production declined to less than 40% of the initial value during the training session, muscle endurance, and mitochondrial content and respiratory capacity, were increased to a similar extent. In contrast, the rate of torque decline during the training session was more pronounced in the Hi30 group compared with the Lo30 group. In response, the Hi30 group, but not the Lo30 group, exhibited increased fatigue resistance and mitochondrial respiration, which was accompanied by increased peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) expression and an activation of AMP-activated protein kinase (AMPK)/unc-51-like autophagy activating kinase 1 (Ulk1) pathway. These data suggest that the frequency of contractions is a critical factor in determining the efficient enhancement of mitochondrial respiratory capacity and muscle endurance through high-intensity training, presumably due to promotion of mitochondrial quality control.<b>NEW & NOTEWORTHY</b> We investigated how training programs varying in contraction frequencies impact the endurance capacity of mouse skeletal muscle, using in vivo supramaximal electrical stimulation to ensure maximal activation of all muscle fibers. Increasing the frequency of contractions during high-intensity training led to increased fatigue resistance and mitochondrial respiratory capacity with fewer repetitions per training session, highlighting the pivotal importance of contraction frequency during exercise training in shaping endurance adaptations in skeletal muscle.