Duchenne Muscular dystrophy and its murine model, mdx, are characterized by Ca2+ induced muscle damage probably due to increased Ca2+ influx through sarcolemmal cation channels. We recently showed that 5 members of the TRP channel superfamily are expressed in skeletal muscle of mice. To investigate the role of TRP channels in the early differentiation of dystrophin- deficient muscle we studied gene expression of TRP channels in the SC-5, immortalized mdx, and the IMO, immortalized, dystrophin-positive cell lines. TaqMan-RT-PCR analyses of TRP channel transcripts showed increased expression of TRPC3 and TRPM4 in both muscle cell lines during 6 d of differentiation. However, mRNA levels of TRPC3, TRPV4 and TRPM7 were much reduced in mdx cells reaching only 10-30% of the level of controls. When the cultures were exposed to low extra-cellular Ca2+ during differentiation, TRPC3 expression increased 4-10 fold in mdx cells within 72 h, but remained nearly unchanged in the controls. We suggest that TRPC3 and TRPM4 channels may play a role for cell fusion or differentiation of myoblasts. Downregulation of TRPC3 in the mdx cell line may reflect an early phenotype of dystrophin-deficiency in culture. The up- regulation of TRPC3 expression under low extracellular Ca2+ points to a Ca2+-dependet regulation of TRPC3 expression in skeletal muscle. (Supported by BMBF, MD-Net project R14)