The expression of subunit genes of the Ca2+ channel complex was studied in differentiating, immortalized mouse mdg cells. These cells expressed alpha 1 and alpha 2/delta transcripts of the skeletal muscle Ca2+ channel genes, a cardiac Ca2+ channel alpha 1 subunit gene and several known transcript variants of skeletal, cardiac and brain beta genes. The mdg mutation is retained in the 129DA3 cell line and occurs exclusively at nucleotide position 4010 in the skeletal alpha 1 transcript in which a cytosine residue is deleted. In early stages of differentiation and fusion, Ba2+ currents were detected in dysgenic myotubes the same as the cardiac L-type Ca2+ channel. These data provide specific structural evidence [Chaudhari, N. (1992) J. Biol. Chem. 267, 25636-25639] for the major genetic defect in mouse muscular dysgenesis and show a change in the expression levels of alpha 1S and alpha 1C. The upregulation of the expression of alpha 1C results in functional Ca2+ channel activity, however, presumably not sufficient for excitation-contraction coupling.