Transient receptor potential (TRP) ion channels serve as cellular sensors and contribute to intracellular Ca2+ regulation in many cell types. Their dysfunction may disturb cellular Ca2+ homeostasis, alter gene expression and lead to degenerative diseases. We recently observed that 7 out of 20 tested members of the TRP channel superfamily are expressed in the skeletal muscle cell line C2C12. To study a possible role of TRP channels in muscle differentiation we investigated their expression levels and cellular localization by TaqMan-RT-PCR and immunohistochemistry, respectively. During differentiation mRNA levels coding for SCN4A, RyR1 and dystrophin rose 60 to 190-fold, indicating muscle specific differentiation. In the same phase expression levels of TRPC1, TRPC6, TRPV2 and TRPM7 remained nearly constant. TRPV4 mRNA level decreased to less than 20% of control while TRPM4 mRNA was transiently 7-fold upregulated during differentiation. Immunohistochemical analyses of TRPC6, TRPV4 and TRPM7 proteins showed cytoplasmic staining close to the nucleus. This staining pattern remained constant during proliferation and muscle differentiation. We suggest that TRPC1, C6, TRPV2 and TRPM7 cation channels play a role for the intracellular Ca2+ regulation of skeletal muscle cells. TRPM4 may be important for cell fusion or differentiation of myoblast (Supported by BMBF, MD-Net project R14).