Na+ -transport modulation induces isoform-specific expression of Na+,K+ -Atpase alpha-subunit isoforms in C2C12...

Changes in demands for Na+ transport alter expression of the Na+,K+ -ATPase subunit isoforms. In skeletal muscle, the effects of these changes on expression the alpha2 isoform, the major isoform expressed in differentiated muscle cell, is not known. Therefore, this study examines regulation of the alpha-subunit isoforms by Na+ in the C2C12 skeletal muscle cell that expresses the alpha1 and alpha2 isoforms. Western blot analysis showed that in differentiating C2C12 muscle cell, but not in undifferentiated myoblast, veratridine, a Na+ channel activator, greatly increased expression of the alpha2 isoform; expression of alpha1 was unaltered. Because the level of alpha-actinin was unaltered, the data suggest that veratridine treatment did not significantly alter the progression of cell differentiation. Furthermore, a reduction in Na+ transport by tetrodotoxin again failed to alter expression of alpha1. Thus, in C2C12 skeletal muscle cell, changes in Na+ transport alters expression of the alpha2, but not the alpha1 isoform. These results differ from those observed previously in muscle cells that express only the alpha1 isoform. Because mammalian skeletal muscle expresses both the alpha1- and alpha2-subunit isoforms, the differential regulation that was observed may be physiologically relevant in these muscle cells in vivo.