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Previously we isolated a μ-calpain/PKCα complex from skeletal muscle which suggested tight interactions between the Ca$^2+$-dependent protease and the kinase in this tissue. Our previous studies also underlined the involvement of ubiquitous calpains in muscular fusion and differentiation. In order to precise the relationships between PKCα and ubiquitous calpains in muscle cells, the expression of these two enzymes was first examined during myogenesis of embryonic myoblasts in culture.Our results show that calpains and PKCα are both present in myotubes and essentially localized in the cytosolic compartment. Moreover, calpains were mainly present after 40 h of cell differentiation concomitantly with a depletion of PKCα content in the particulate fraction and the appearance of PKMα fragment. These results suggest a possible calpain dependent down-regulation process of PKCαa in our model at the time of intense fusion.In our experimental conditions phorbol myristate acetate (PMA) induced a rapid depletion of pkcα in the cytosolic fraction and its translocation toward the particulate fraction. Long term exposure of myotubes in the presence of PMA induced down-regulation of PKCα, this process being partially blocked by calpain inhibitors (CS peptide and inhibitor II) and antisense oligonucleotides for the two major ubiquitous calpain isoforms (m- and μ-calpains).Taken together, our findings argue for an involvement of calpains in the differentiation of embryonic myoblasts by limited proteolytic cleavage of PKCα.