RESTORATION OF NORMAL ULTRASTRUCTURE AFTER EXPRESSION OF THE ALPHA-1 SUBUNIT OF THE L-TYPE CA2+ CHANNEL IN DYSGENIC MYOTUBES

Muscular dysgenesis (mdg) is a spontaneous mutation affecting the alpha 1 subunit of the skeletal L-type Ca2+ channel. mdg/mdg mice suffer from a skeletal muscle disease characterised by low levels of the slow Ca2+ current, lack of contractile activity, and immature organisation of skeletal muscle. Microinjections of a cDNA encoding al into mutant myotubes restore excitation-contraction coupling. We checked here that dysgenic myotubes transfected with expression vectors, including a full-length alpha 1 cDNA, also recover normal ultrastructural features. Transfection of alpha 1 cDNA partially deleted on the 5' end leads to the recovery of a good structural organisation without any improvement in the mutant physiological phenotype. These results suggest that: (i) the proper expression of alpha 1 is required for the full muscle differentiation of muscular dysgenesis myotubes, and (ii) portions of the alpha 1 molecule may be involved in the structural organisation of a muscle fiber, independent of its known functional properties.