TY - JOUR
T1 - Voltage-dependent Na+ channel phenotype changes in myoblasts. Consequences for cardiac repair
AU - Martínez-Mármol, Ramón
AU - David, Miren
AU - Sanches, Rosario
AU - Roura-Ferrer, Meritxell
AU - Villalonga, Núria
AU - Sorianello, Eleonora
AU - Webb, Susan M.
AU - Zorzano, Antonio
AU - Gumà, Anna
AU - Valenzuela, Carmen
AU - Felipe, Antonio
PY - 2007/12/1
Y1 - 2007/12/1
N2 - 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 (Nav) 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 Nav 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 Nav1.4 and Nav1.5, although neither protein has an apparent role in cell growth. During myogenesis, Nav1.5 was largely induced. Electrophysiological and pharmacological properties, as well as mRNA expression, indicate that cardiac-type Nav1.5 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 Nav1.5 colocalization in caveolae. Finally, we demonstrate that the treatment of myoblasts with neuregulin further increased Nav1.5 in skeletal myocytes. Conclusion: Our results indicate that skeletal myotubes adopt a cardiac-like phenotype in cell culture conditions and that the expression of Nav1.5 acts as an underlying molecular mechanism. © 2007 Elsevier B.V. All rights reserved.
AB - 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 (Nav) 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 Nav 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 Nav1.4 and Nav1.5, although neither protein has an apparent role in cell growth. During myogenesis, Nav1.5 was largely induced. Electrophysiological and pharmacological properties, as well as mRNA expression, indicate that cardiac-type Nav1.5 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 Nav1.5 colocalization in caveolae. Finally, we demonstrate that the treatment of myoblasts with neuregulin further increased Nav1.5 in skeletal myocytes. Conclusion: Our results indicate that skeletal myotubes adopt a cardiac-like phenotype in cell culture conditions and that the expression of Nav1.5 acts as an underlying molecular mechanism. © 2007 Elsevier B.V. All rights reserved.
KW - Cardiac repair
KW - Cardiomyoplasty
KW - Myogenesis
KW - Skeletal myoblast
KW - Sodium channels
U2 - https://doi.org/10.1016/j.cardiores.2007.08.009
DO - https://doi.org/10.1016/j.cardiores.2007.08.009
M3 - Article
VL - 76
SP - 430
EP - 441
JO - Cardiovascular Research
JF - Cardiovascular Research
SN - 0008-6363
ER -