title: Myotonic dystrophy kinase modulates skeletal muscle but not cardiac voltage-gated sodium channels.
abstract: Altered modulation of skeletal muscle voltage-gated sodium channels by myotonic dystrophy kinase (DMPK) has been proposed as a possible mechanism underlying myotonia in this disease. We examined the effect of a recombinant mouse DMPK on the functional properties of human skeletal muscle (hSkM1) and cardiac (hH1) voltage-gated sodium channels in the Xenopus oocyte expression system. Co-expression of DMPK with hSkM1 in oocytes resulted in significantly lower peak sodium current amplitude as compared to cells expressing hSkM1 alone in agreement with a previous report. By contrast, DMPK had no effect on the level of expressed sodium current in cells expressing hH1. Similarly, there were no measurable effects of the kinase on the kinetics or steady-state properties of activation or inactivation. Our findings support the previous observations made with rat muscle sodium channels and demonstrate that the effect of DMPK on sodium channels is isoform specific despite conservation of a putative phosphorylation site between the two isoforms.
authors.affiliation: Centre de Recherche, Hôpital Laval, Sainte-Foy, Quebec, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Chahine
authors.forename: A L
authors.initials: AL
authors.lastname: George
mesh_terms: D000818:Animals; D006801:Humans; D015640:Ion Channel Gating; D051379:Mice; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology*; D009223:Myotonic Dystrophy / Q000201:enzymology* / Q000503:physiopathology; D065636:Myotonin-Protein Kinase; D009865:Oocytes; D018408:Patch-Clamp Techniques; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D014981:Xenopus
chemical_list: C585517:DMPK protein, human; C585516:DMPK protein, mouse; D015222:Sodium Channels; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases