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 myoblasts have different electrophysiological properties than cardiocytes, however, may considerably limit the success of this therapy. In particular, myoblast electrophysiological features do not allow for proper cardiac-like impulse conduction and synchronous contraction of the skeletal graft with cardiac host tissue. "Electrophysiological transformation" of myoblasts into cardiocytes- if possible- would be a means to overcome this problem. Here we report that treatment of mouse C2C12 skeletal muscle cells with differentiation medium preconditioned by cardiocytes significantly altered their sodium current activation and inactivation properties from skeletal muscle- to more cardiac-like ones. A reduced tetrodotoxin sensitivity of cardiac-conditioned cell currents and RT-PCR experiments suggest that an up-regulation of the expression of the cardiac sodium channel isoform Nav1.5 is responsible for the observed changes in sodium current function. We conclude that cardiocytes induce cardiac sodium channel expression in skeletal muscle cells via a paracrine mechanism. Electrophysiological transformation of skeletal muscle cells into cardiocytes, thus, seems possible. Supported by Austrian FWF, P-15063