| First Author | Watanabe D | Year | 2024 |
| Journal | Am J Physiol Cell Physiol | Volume | 326 |
| Issue | 3 | Pages | C795-C809 |
| PubMed ID | 38223925 | Mgi Jnum | J:345643 |
| Mgi Id | MGI:7610381 | Doi | 10.1152/ajpcell.00440.2023 |
| Citation | Watanabe D, et al. (2024) Ca(2+) storage function is altered in the sarcoplasmic reticulum of skeletal muscle lacking mitsugumin 23. Am J Physiol Cell Physiol 326(3):C795-C809 |
| abstractText | 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(2+) storage function in skeletal muscle by using Mg23-knockout (Mg23(-/-)) mice. There was no difference in the isometric specific force of the extensor digitorum longus (EDL) and soleus (SOL) muscles between Mg23(-/-) and wild-type (Wt) mice. In Mg23(-/-) mice, the calsequestrin 2 content in the EDL muscle and SR Ca(2+)-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(2+), which showed that Mg23(-/-) mice, compared with Wt, had: 1) elevated total Ca(2+) content in the membranous components including SR, mitochondria, and transverse tubular system referred to as endogenous Ca(2+) content, in both type I and II fibers of the EDL and SOL; 2) increased maximal Ca(2+) content in both type I and II fibers of the EDL and SOL; 3) decreased SR Ca(2+) leakage in type I fibers of the SOL; and 4) enhanced SR Ca(2+) 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(2+) storage in both type I and type II fibers, likely due to increased SR Ca(2+) leakage.NEW & NOTEWORTHY 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(2+) storage in skeletal muscle fibers. These findings provide valuable insights into the physiological regulation of Ca(2+) in skeletal muscle, offering significant potential for uncovering the mechanisms underlying muscle fatigue, muscle adaptation, and muscle diseases. |
