DEFICIENCY OF NA+ K+-ATPASE AND SARCOPLASMIC-RETICULUM CA2+-ATPASE INSKELETAL-MUSCLE AND CULTURED MUSCLE-CELLS OF MYOTONIC-DYSTROPHY PATIENTS/

Since defective regulation of ion transport could initiate or contribu te to the abnormal cellular function in myotonic dystrophy (MyD), Na+/ K+-ATPase and sarcoplasmic reticulum (SR) Ca2+-ATPase were examined in skeletal muscle and cultured skeletal muscle cells of controls and My D patients. Na+/K+-ATPase was investigated by measuring ouabain bindin g and the activities of Na+/K+-ATPase and K+-dependent 3-O-methylfluor escein phosphate (3-O-MFPase). SR Ca2+-ATPase was analysed by e.l.i.s. a., Ca2+-dependent phosphorylation and its activities with ATP and 3-O -methylfluorescein phosphatase (3-O-MFP). In MyD muscle the K+-depende nt 3-O-MFPase activity and the activity and concentration of SR Ca2+-A TPase were decreased by 40 %. In cultured muscle cells from MyD patien ts the activities as well as the concentration of both Na+/K+-ATPase a nd SR Ca2+-ATPase were reduced by about 30-40%. The ouabain-binding co nstant and the molecular activities, i.e. catalytic-centre activities with ATP or 3-O-MFP, of Na+/K+-ATPase and SR Ca2+-ATPase were similar in muscle as well as in cultured cells from both controls and MyD pati ents. Thus the decreased activity of both ATPases in MyD muscle is cau sed by a reduction in the number of their molecules. To check whether the deficiency of ATP-dependent ion pumps is a general feature of the pathology of MyD, we examined erythrocytes from the same patients. In these cells the Ca2+ uptake rate and the Ca2+-ATPase activity were low er than in controls, but the Ca2+-ATPase concentration was normal. Thu s the reduced Ca2+-ATPase activity is caused by a decrease in the mole cular activity of the ion pump. The Na+/K+-ATPase activity is also low er in erythrocytes of MyD patients. It is concluded that the observed alterations in ion pumps may contribute to the pathological phenomena in the muscle and other tissues in patients with MyD.