Aims: 

Intra-cardiac transplantation of skeletal 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 myocytes adopt more cardiac-like electrophysiological properties.

Methods: 

To test if a cardiac cell environment can indeed modify electrophysiological parameters of skeletal myocytes, we treated mouse C2C12 myocytes with medium preconditioned by primary cardiocytes and compared their functional sodium current properties with those of control cells using the whole cell patch clamp technique.

Results: 

This treatment significantly altered the activation and inactivation properties of sodium currents from "skeletal muscle"- to more "cardiac"-like ones. Reverse transcription PCR experiments suggest that an up-regulation 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.

Conclusion: 

Cardiomyocytes alter sodium channel isoform expression of skeletal myocytes via a paracrine mechanism. Thereby, skeletal myocytes with more cardiac-like sodium current properties are generated.

Supported by Austrian FWF (P-15063).