Electrical stimulation modulates IGF binding protein transcript levels in C2C12 myotubes

Electrical stimulation (ES) of skeletal muscle can produce changes in metabolic enzyme and contractile protein gene expression resulting in fast-to-slow phenotypic changes. The molecular mechanism by which ES induces changes in phenotype is not entirely understood but recent reports have demonstrated that the calcineurin/NF-AT signalling pathway is involved. IGF-1 is also capable of inducing changes in phenotype through the same calcineurin/NF-AT pathway but little is known of the direct effect of ES on the IGF system. In this study, we examined the effects of ES on the expression of igf-1, igf-2 and the six igfbp genes in the C2C12 muscle cell line. Results showed that ES induced a change in phenotype that was accompanied by downregulation of igf-2 and upregulation of igfbp-4 mRNA levels. However, ES did not significantly alter the transcription of igf-1, igfbp-2, igfbp-5 and igfbp-6 genes. This study demonstrates that ES of muscle cells in vitro not only directly modulates the gene expression of contractile proteins but also modulates proteins that are part of the IGF regulatory system, in particular IGFBP-4.