{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T15:55:21Z","timestamp":1761666921953,"version":"build-2065373602"},"reference-count":62,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2005,12,1]],"date-time":"2005-12-01T00:00:00Z","timestamp":1133395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2005,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Mechanosensitive cation channels (MSC) are ubiquitous in eukaryotic cell types. However, the physiological functions of MSC in several tissues remain in question. In this study we have investigated the role of MSC in skeletal myogenesis. Treatment of C2C12 myoblasts with gadolinium ions (MSC blocker) inhibited myotube formation and the myogenic index in differentiation medium (DM). The enzymatic activity of creatine kinase (CK) and the expression of myosin heavy chain\u2010fast twitch (MyHCf) in C2C12 cultures were also blocked in response to gadolinium. Treatment of C2C12 myoblasts with gadolinium ions did not affect the expression of either cyclin A or cyclin D1 in DM. Other inhibitors of MSC such as streptomycin and GsTMx\u20104 also suppressed the expression of CK and MyHCf in C2C12 cultures. The inhibitory effect of gadolinium ions on myogenic differentiation was reversible and independent of myogenic cell type. Real\u2010time\u2010polymerase chain reaction analysis revealed that inhibition of MSC decreases the expression of myogenic transcription factors MyoD, myogenin, and Myf\u20105. Furthermore, the activity of skeletal \u03b1\u2010actin promoter was suppressed on MSC blockade. Treatment of C2C12 myoblasts with gadolinium ions prevented differentiation\u2010associated cell death and inhibited the cleavage of poly (ADP\u2010ribose) polymerase and activation of caspase\u20103. On the other hand, delivery of active caspase\u20103 protein to C2C12 myoblasts reversed the inhibitory effect of gadolinium ions on myogenesis. Our data suggest that inhibition of MSC suppresses myogenic differentiation by inhibiting the caspase\u20103 activity and the expression of myogenic regulatory factors.\u2014Wedhas, N., Klamut, H. J., Dogra, C., Srivastava, A. K., Mohan, S., Kumar, A. Inhibition of mechanosensitive cation channels inhibits myogenic differentiation by suppressing the expression of myogenic regulatory factors and caspase\u20103 activity.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    19, 1986\u20131997 (2005)\n                  <\/jats:p>","DOI":"10.1096\/fj.05-4198com","type":"journal-article","created":{"date-parts":[[2005,11,30]],"date-time":"2005-11-30T18:58:43Z","timestamp":1133377123000},"page":"1986-1997","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Inhibition of mechanosensitive cation channels inhibits myogenic differentiation by suppressing the expression of myogenic regulatory factors and caspase\u20103 activity"],"prefix":"10.1096","volume":"19","author":[{"given":"Nia","family":"Wedhas","sequence":"first","affiliation":[{"name":"Molecular Genetics Division Musculoskeletal Disease Center Jerry L. 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