HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Am J Physiol Heart Circ Physiol 292: H439-H450, 2007. First published September 15, 2006; doi:10.1152/ajpheart.00119.2006
0363-6135/07 $8.00

This Article Free upon publication Full Text Full Text (PDF) All Versions of this Article: 292/1/H439    most recent 00119.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Zebedin, E. Articles by Hilber, K. Search for Related Content PubMed PubMed Citation Articles by Zebedin, E. Articles by Hilber, K.

C₂C₁₂ skeletal muscle cells adopt cardiac-like sodium current properties in a cardiac cell environment

Center of Biomolecular Medicine and Pharmacology, Institute of Pharmacology, Medical University of Vienna, Vienna, Austria

Submitted 1 February 2006 ; accepted in final form 7 September 2006

Intracardiac transplantation of undifferentiated skeletal muscle cells (myoblasts) has emerged as a promising therapy for myocardial infarct repair and is already undergoing clinical trials. The fact that cells originating from skeletal muscle have different electrophysiological properties than cardiomyocytes, however, may considerably limit the success of this therapy and, in addition, cause side effects. Indeed, a major problem observed after myoblast transplantation is the occurrence of ventricular arrhythmias. The most often transient nature of these arrhythmias may suggest that, once transplanted into cardiac tissue, skeletal muscle cells adopt more cardiac-like electrophysiological properties. To test whether a cardiac cell environment can indeed modify electrophysiological parameters of skeletal muscle cells, we treated mouse C₂C₁₂ myocytes with medium preconditioned by primary cardiocytes and compared their functional sodium current properties with those of control cells. We found this treatment to significantly alter the activation and inactivation properties of sodium currents from "skeletal muscle" to more "cardiac"-like ones. Sodium currents of cardiac-conditioned cells showed a reduced sensitivity to block by tetrodotoxin. These findings and reverse transcription PCR experiments suggest that an upregulation of the expression of the cardiac sodium channel isoform Na_v1.5 versus the skeletal muscle isoform Na_v1.4 is responsible for the observed changes in sodium current function. We conclude that cardiomyocytes alter sodium channel isoform expression of skeletal muscle cells via a paracrine mechanism. Thereby, skeletal muscle cells with more cardiac-like sodium current properties are generated.

sodium channel isoform expression; myoblast transplantation

This article has been cited by other articles:

				R. Martinez-Marmol, M. David, R. Sanches, M. Roura-Ferrer, N. Villalonga, E. Sorianello, S. M. Webb, A. Zorzano, A. Guma, C. Valenzuela, et al. Voltage-dependent Na+ channel phenotype changes in myoblasts. Consequences for cardiac repair Cardiovasc Res, December 1, 2007; 76(3): 430 - 441. [Abstract] [Full Text] [PDF]