title: Ion transport in human skeletal muscle cells: disturbances in myotonic dystrophy and Brody's disease.
abstract: After excitation of skeletal muscle, the disturbed ion homeostasis is restored by Na+, K+ ATPase of the sarcolemma and Ca2+ ATPase of the sarcoplasmic reticulum (SR). Contrary to Na+, K+ ATPase, the concentration and isoenzyme distribution of SR Ca2+ ATPase in human skeletal muscle depend on fibre type and age. In cultured human muscle cells the concentration and activity of Na+, K+ ATPase and SR Ca2+ ATPase increase with maturation. In skeletal muscle and cultured muscle cells of patients suffering from myotonic dystrophy (MyD), the activity and the concentration of both Na+, K+ ATPase and SR Ca2+ ATPase are decreased by about 40%. In addition, we measured in cultured MyD muscle cells at rest an increased cytosolic Ca2+ concentration ([Ca2+]i) caused by active voltage-operated Ca2+ channels, which are inactive in resting control cells. However, the restoration of a stimulus-induced Ca2+ transient is unaffected. A differentiation-related disturbance of membranes or a modulation defect of membrane proteins may play a role in MyD. In skeletal muscle and cultured muscle cells of patients suffering from Brody's disease, which is characterized by impaired muscle relaxation, the SR Ca2+ ATPase activity is reduced by about 50%, but the concentrations of total SR Ca2+ ATPase and the predominant SERCA1 isoform are normal. Diseased muscle cells show a delayed restoration of [Ca2+]i after stimulation, which might be explained by structural modifications of SERCA1. Reduction of the Ca2+ release by drugs balances the excitation-relaxation cycle of the pathological cells.
authors.affiliation: Department of Biochemistry, University of Nijmegen, The Netherlands.
authors.forename: A A
authors.initials: AA
authors.lastname: Benders
authors.forename: R A
authors.initials: RA
authors.lastname: Wevers
authors.forename: J H
authors.initials: JH
authors.lastname: Veerkamp
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D000293:Adolescent; D000328:Adult; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D003620:Dantrolene / Q000494:pharmacology; D005260:Female; D006706:Homeostasis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009136:Muscular Dystrophies / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000172:deficiency*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D009125:Muscle Relaxants, Central; D011189:Potassium Chloride; D014700:Verapamil; D000254:Sodium-Potassium-Exchanging ATPase; D003620:Dantrolene; D009543:Nifedipine; D000109:Acetylcholine; D002118:Calcium