MYOTONIC-DYSTROPHY PROTEIN-KINASE IS INVOLVED IN THE MODULATION OF THE CA2-MUSCLE CELLS( HOMEOSTASIS IN SKELETAL)

Myotonic dystrophy (DM), the most prevalent muscular disorder in adult s, is caused by (CTG)(n)-repeat expansion in a gene encoding a protein kinase (DM protein kinase; DMPK) and involves changes in cytoarchitec ture and ion homeostasis. To obtain clues to the normal biological rol e of DMPK in cellular ion homeostasis, we have compared the resting [C a2+](i), the amplitude and shape of depolarization-induced Ca2+ transi ents, and the content of ATP-driven ion pumps in cultured skeletal mus cle cells of wild-type and DMPK[-/-] knockout mice. In vitro-different iated DMPK[-/-] myotubes exhibit a higher resting [Ca2+](i), than do w ild-type myotubes because of an altered open probability of voltage-de pendent L-type Ca2+ and Na+ channels. The mutant myotubes exhibit smal ler and slower Ca2+ responses upon triggering by acetylcholine or high external K+. In addition, we observed that these Ca2+ transients part ially result from an influx of extracellular Ca2+ through the L-type C a2+ channel, Neither the content nor the activity of Na+/K+ ATPase and sarcoplasmic reticulum Ca2+-ATPase are affected by DMPK absence. In c onclusion, our data suggest that DMPK is involved in modulating the in itial events of excitation-contraction coupling in skeletal muscle.