ORCID Profile
0000-0003-3929-1960
Current Organisation
Instituto de Investigaciones Biomédicas Alberto Sols
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Publisher: Elsevier BV
Date: 04-2008
DOI: 10.1016/J.BBRC.2008.01.138
Abstract: Voltage-gated sodium channels (Na(v)) consist of a pore-forming alpha subunit (Na(v)alpha) associated with beta regulatory subunits (Na(v)beta). Adult skeletal myocytes primarily express Na(v)1.4 channels. We found, however, using neonatal L6E9 myocytes, that myofibers acquire a Na(v)1.5-cardiac-like phenotype efficiently. Differentiated myotubes elicited faster Na(v)1.5 currents than those recorded from myoblasts. Unlike myoblasts, I(Na) recorded in myotubes exhibited an accumulation of inactivation after the application of trains of pulses, due to a slower recovery from inactivation. Since Na(v)beta subunits modulate channel gating and pharmacology, the goal of the present work was to study Na(v)beta subunits during myogenesis. All four Na(v)beta (Na(v)beta1-4) isoforms were present in L6E9 myocytes. While Na(v)beta1-3 subunits were up-regulated by myogenesis, Na(v)beta4 subunits were not. These results show that Na(v)beta genes are strongly regulated during muscle differentiation and further support a physiological role for voltage-gated Na(+) channels during development and myotube formation.
Publisher: Elsevier BV
Date: 05-2008
DOI: 10.1016/J.BBAMCR.2008.01.001
Abstract: Voltage-dependent K(+) channels (Kv) are involved in the proliferation of many types of cells, but the mechanisms by which their activity is related to cell growth remain unclear. Kv antagonists inhibit the proliferation of mammalian cells, which is of physiological relevance in skeletal muscle. Although myofibres are terminally differentiated, some resident myoblasts may re-enter the cell cycle and proliferate. Here we report that the expression of Kv1.5 is cell-cycle dependent during myoblast proliferation. In addition to Kv1.5 other Kv, such as Kv1.3, are also up-regulated. However, pharmacological evidence mainly implicates Kv1.5 in myoblast growth. Thus, the presence of S0100176, a Kv antagonist, but not margatoxin and dendrotoxin, led to cell cycle arrest during the G(1)-phase. The use of selective cell cycle blockers showed that Kv1.5 was transiently accumulated during the early G(1)-phase. Furthermore, while myoblasts treated with S0100176 expressed low levels of cyclin A and D(1), the expression of p21(cip-1) and p27(kip1), two cyclin-dependent kinase inhibitors, increased. Our results indicate that the cell cycle-dependent expression of Kv1.5 is involved in skeletal muscle cell proliferation.
Publisher: Elsevier BV
Date: 06-2012
Publisher: Oxford University Press (OUP)
Date: 12-2007
DOI: 10.1016/J.CARDIORES.2007.08.009
Abstract: 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. 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(v)1.5 was largely induced. Electrophysiological and pharmacological properties, as well as mRNA expression, indicate that cardiac-type Na(v)1.5 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 Na(v)1.5 colocalization in caveolae. Finally, we demonstrate that the treatment of myoblasts with neuregulin further increased Na(v)1.5 in skeletal myocytes. Our results indicate that skeletal myotubes adopt a cardiac-like phenotype in cell culture conditions and that the expression of Na(v)1.5 acts as an underlying molecular mechanism.
Location: Spain
Location: Spain
Location: Mexico
Location: United States of America
Location: Spain
No related grants have been discovered for Carmen Valenzuela.