title: C2C12 skeletal muscle cells adopt cardiac-like sodium current properties in a cardiac cell environment.
abstract: 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 C(2)C(12) 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(v)1.5 versus the skeletal muscle isoform Na(v)1.4 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.
authors.affiliation: Center of Biomolecular Medicine and Pharmacology, Institute of Pharmacology, Medical Univ. of Vienna, Waehringerstrasse 13A, A-1090 Vienna, Austria.
authors.forename: Eva
authors.initials: E
authors.lastname: Zebedin
authors.forename: Markus
authors.initials: M
authors.lastname: Mille
authors.forename: Maria
authors.initials: M
authors.lastname: Speiser
authors.forename: Touran
authors.initials: T
authors.lastname: Zarrabi
authors.forename: Walter
authors.initials: W
authors.lastname: Sandtner
authors.forename: Birgit
authors.initials: B
authors.lastname: Latzenhofer
authors.forename: Hannes
authors.initials: H
authors.lastname: Todt
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Hilber
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D015640:Ion Channel Gating / Q000502:physiology*; D051379:Mice; D032448:Myoblasts, Skeletal / Q000166:cytology* / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology*; D019899:Paracrine Communication / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000145:classification / Q000502:physiology*
chemical_list: D015222:Sodium Channels