Intrinsic contractile dysfunction due to impaired sarcoplasmic reticulum Ca²⁺ release in compensatory hypertrophied muscle fibers following synergist ablation

Synergist ablation (SA) has widely been used to understand the mechanisms behind skeletal muscle hypertrophy. However, compensatory hypertrophied muscles display intrinsic contractile dysfunction, i.e., a hallmark of overuse. Here, we demonstrate that SA-induced compensatory hypertrophy is accompanied by muscle weakness due to impaired sarcoplasmic reticulum Ca 2+ release. This dysfunction may be caused by the degradation of triad proteins due to the reciprocal amplification of reactive oxygen species and Ca 2+ signaling at the junctional space microdomain.