title: Myotonic dystrophy protein kinase is involved in the modulation of the Ca2+ homeostasis in skeletal muscle cells.
abstract: Myotonic dystrophy (DM), the most prevalent muscular disorder in adults, is caused by (CTG)n-repeat expansion in a gene encoding a protein kinase (DM protein kinase; DMPK) and involves changes in cytoarchitecture and ion homeostasis. To obtain clues to the normal biological role of DMPK in cellular ion homeostasis, we have compared the resting [Ca2+]i, the amplitude and shape of depolarization-induced Ca2+ transients, and the content of ATP-driven ion pumps in cultured skeletal muscle cells of wild-type and DMPK[-/-] knockout mice. In vitro-differentiated DMPK[-/-] myotubes exhibit a higher resting [Ca2+]i than do wild-type myotubes because of an altered open probability of voltage-dependent l-type Ca2+ and Na+ channels. The mutant myotubes exhibit smaller and slower Ca2+ responses upon triggering by acetylcholine or high external K+. In addition, we observed that these Ca2+ transients partially result from an influx of extracellular Ca2+ through the l-type Ca2+ channel. Neither the content nor the activity of Na+/K+ ATPase and sarcoplasmic reticulum Ca2+-ATPase are affected by DMPK absence. In conclusion, our data suggest that DMPK is involved in modulating the initial events of excitation-contraction coupling in skeletal muscle.
authors.affiliation: Department of Biochemistry, University of Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: A A
authors.initials: AA
authors.lastname: Benders
authors.forename: P J
authors.initials: PJ
authors.lastname: Groenen
authors.forename: F T
authors.initials: FT
authors.lastname: Oerlemans
authors.forename: J H
authors.initials: JH
authors.lastname: Veerkamp
authors.forename: B
authors.initials: B
authors.lastname: Wieringa
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002478:Cells, Cultured; D006706:Homeostasis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009223:Myotonic Dystrophy / Q000378:metabolism*; D065636:Myotonin-Protein Kinase; D009543:Nifedipine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; C585516:DMPK protein, mouse; D012433:Ryanodine; D013779:Tetrodotoxin; D011189:Potassium Chloride; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D009543:Nifedipine; D000109:Acetylcholine; D002118:Calcium