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Voltage-dependent Na+ channel phenotype changes in myoblasts. Consequences for cardiac repair
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Objective: Cellular cardiomyoplasty using skeletal myoblasts is a promising therapy for myocardial infarct repair. Once transplanted, myoblasts grow, differentiate and adapt their electrophysiological properties towards more cardiac-like phenotypes. Voltage-dependent Na + channels (Na v ) are the main proteins involved in the propagation of the cardiac action potential, and their phenotype affects cardiac performance. Therefore, we examined the expression of Na v during proliferation and differentiation in skeletal myocytes. Methods and results: We used the rat neonatal skeletal myocyte cell line L6E9. Proliferation of L6E9 cells induced Na v 1.4 and Na v 1.5, although neither protein has an apparent role in cell growth. During myogenesis, Na v1.5 was largely induced. Electrophysiological and pharmacological properties, as well as mRNA expression, indicate that cardiac-type Na v1.5 accounts for almost 90% of the Na + current in myotubes. Unlike in proliferation, this protein plays a pivotal role in myogenesis. The adoption of a cardiac-like phenotype is further supported by the increase in Nav 1.5 colocalization in caveolae. Finally, we demonstrate that the treatment of myoblasts with neuregulin further increased Na v 1.5 in skeletal myocytes. Conclusion: Our results indicate that skeletal myotubes adopt a cardiac-like phenotype in cell culture conditions and that the expression of Na v1.5 acts as an underlying molecular mechanism.
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MARTÍNEZ-MÁRMOL, Ramón, DAVID, Miren, SANCHES, Rosario, ROURA-FERRER, Meritxell, VILLALONGA, Núria, SORIANELLO, Eleonora, WEBB, Susan m., ZORZANO OLARTE, Antonio, GUMÀ I GARCIA, Anna maria, VALENZUELA, Carmen, FELIPE CAMPO, Antonio. Voltage-dependent Na+ channel phenotype changes in myoblasts. Consequences for cardiac repair. _Cardiovascular Research_. 2007. Vol. 76, núm. 3, pàgs. 430-441. [consulta: 23 de març de 2026]. ISSN: 0008-6363. [Disponible a: https://hdl.handle.net/2445/197083]