Physiological Muscle Function Is Controlled by the Skeletal Endocannabinoid System in Murine Skeletal Muscles

The endocannabinoid system (ECS) regulates and controls many of our most critical bodily functions including healthy muscles however, its potential role(s) in physiological skeletal muscle function and its disorders are unclear. Earlier using the Cre/LoxP system we generated and characterized a tamoxifen-inducible skel-etal muscle-specific CB1R knockdown (skmCB1-KD) mouse model. Here, we sought to elucidate the mechanisms underlying reduced muscle force generation. To address this, we measured calcium movements following electrical stimula-tion-induced muscle fatigue, evaluated store-operated calcium entry (SOCE), and conducted functional analysis of respiring mitochondria. Based on our measure-ments, it is likely that the reduced muscle performance recorded in vivo may oc-cur due to complementary changes in ATP production by mitochondria. Further-more, in skmCB1-KD mice, we observed a significant decrease in one component of the respiratory chain and a delayed mitochondrial membrane potential dissipa-tion upon the application of an un-coupler.