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oai:recercat.cat:2445/1970832025-12-04T21:15:14Zcom_2072_1057col_2072_478781col_2072_478917

Voltage-dependent Na+ channel phenotype changes in myoblasts. Consequences for cardiac repair 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 Canals iònics Miogènesi Malalties del cor Biologia del desenvolupament Ion channels Myogenesis Heart diseases Developmental biology 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. 2023-04-21T07:56:28Z 2023-04-21T07:56:28Z 2007-12-01 2023-04-21T07:56:28Z info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion 0008-6363 https://hdl.handle.net/2445/197083 553982 eng Versió postprint del document publicat a: https://doi.org/10.1016/j.cardiores.2007.08.009 Cardiovascular Research, 2007, vol. 76, num. 3, p. 430-441 https://doi.org/10.1016/j.cardiores.2007.08.009 (c) European Society of Cardiology, 2007 info:eu-repo/semantics/openAccess 12 p. application/pdf Oxford University Press Articles publicats en revistes (Bioquímica i Biomedicina Molecular)