Copyright © 2007, European Society of Cardiology
Voltage-dependent Na+ channel phenotype changes in myoblasts. Consequences for cardiac repair*
aMolecular Physiology Laboratory, Universitat de Barcelona, Spain
bDepartament de Bioquímica i Biología Molecular, Universitat de Barcelona, Spain
cParc Cientific de Barcelona, Universitat de Barcelona, Spain
dDepartament de Endocrinologia i Medicina, Hospital Sant Pau, Universitat Autonoma de Barcelona, Spain
eInstituto de Farmacología y Toxicología, CSIC/UCM, Universidad Complutense de Madrid, Spain
*Correspondence author. Molecular Physiology Laboratory, Departament de Bioquímica i Biología Molecular, Universitat de Barcelona, Avda Diagonal 645, E-08028 Barcelona, Spain. Tel.: +34 934034616; fax: +34 934021559. afelipe{at}ub.edu
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.
KEYWORDS Sodium channels; Cardiomyoplasty; Myogenesis; Skeletal myoblast; Cardiac repair
* AF designed research. AZ coordinated human biopsies and contributed with reagents. SMW collected human samples. ES isolated human myoblasts. RMM, MD and CV performed electrophysiology. RMM, RS, MRF, NV undertook research. RS and AG performed NRG experiments. RMM, MD, CV and AF analysed data. AF and CV wrote the paper.