ION-TRANSPORT IN HUMAN SKELETAL-MUSCLE CELLS - DISTURBANCES IN MYOTONIC-DYSTROPHY AND BRODYS DISEASE

After excitation of skeletal muscle, the disturbed ion homeostasis is restored by Na+, K+ ATPase of the sarcolemma and Ca2+ ATPase of the sa rcoplasmic reticulum (SR). Contrary to Na+, K+ ATPase. the concentrati on and isoenzyme distribution of SR Ca2+ ATPase in human skeletal musc le depend on fibre type and age. In cultured human muscle cells the co ncentration and activity of Na+, K+ ATPase and SR Ca2+ ATPase increase with maturation. In skeletal muscle and cultured muscle cells of pati ents suffering from myotonic dystrophy (MyD). the activity and the con centration of both Na+, K+ ATPase and SR Ca2+ ATPase are decreased by about 40%. In addition, we measured in cultured MyD muscle cells at re st an increased cytosolic Ca2+ concentration ([Ca2+](i)) caused by act ive voltage-operated Ca2+ channels, which are inactive in resting cont rol cells. However. ?he restoration of a stimulus-induced Ca2+ transie nt is unaffected. A differentiation-related disturbance of membranes o r a modulation defect of membrane proteins may play a role in MyD. In skeletal muscle and cultured muscle cells of patients suffering from B rody's disease. which is characterized by impaired muscle relaxation, the SR Ca2+ ATPase activity is reduced by about 50%, but the concentra tions of total SR Ca2+ ATPase and the predominant SERCA1 isoform are n ormal. Diseased muscle cells show a delayed restoration of [Ca2+](i) a fter stimulation. which might be explained by structural modifications of SERCA1. Reduction of the Ca2+ release by drugs balances the excita tion-relaxation cycle of the pathological cells.