Ca storage function is altered in the sarcoplasmic reticulum of skeletal muscle lacking mitsugumin 23.

Mitsugumin 23 (MG23) has been identified as a ball-shaped cation channel in the sarcoplasmic reticulum (SR) but its physiological role remains unclear. This study aimed to examine the contribution of MG23 to Ca storage function in skeletal muscle by using -knockout () mice. There was no difference in the isometric specific force of the extensor digitorum longus (EDL) and soleus (SOL) muscles between and wild-type (Wt) mice. In mice, the calsequestrin 2 content in the EDL muscle and SR Ca-ATPase 2 content in the SOL were increased. We have examined SR and myofibril functions using mechanically skinned fibers and determined their fiber types based on the response to Sr, which showed that mice, compared with Wt, had: ) elevated total Ca content in the membranous components including SR, mitochondria, and transverse tubular system referred to as endogenous Ca content, in both type I and II fibers of the EDL and SOL; ) increased maximal Ca content in both type I and II fibers of the EDL and SOL; ) decreased SR Ca leakage in type I fibers of the SOL; and ) enhanced SR Ca uptake in type I fibers of the SOL, although myofibril function was not different in both type I and II fibers of the SOL and EDL muscles. These results suggest that MG23 decreases SR Ca storage in both type I and type II fibers, likely due to increased SR Ca leakage. The function of calcium storage within sarcoplasmic reticulum (SR) plays a pivotal role in influencing the health and disease states of skeletal muscle. In the present study, we demonstrated that mitsgumin 23, a novel non-selective cation channel, modifies SR Ca storage in skeletal muscle fibers. These findings provide valuable insights into the physiological regulation of Ca in skeletal muscle, offering significant potential for uncovering the mechanisms underlying muscle fatigue, muscle adaptation, and muscle diseases.