Effects of age and gene dose on skeletal muscle sodium channel gating in mice deficient in myotonic dystrophy protein kinase.
Myotonic muscular dystrophy (DM) is characterized by abnormal skeletal muscle Na channel gating and reduced levels of myotonic dystrophy protein kinase (DMPK). Electrophysiological measurements show that mice deficient in Dmpk have reduced Na currents in muscle. We now find that the Na channel expression level is normal in mouse muscle partially or completely deficient in Dmpk. Reduced current amplitudes are not changed by age or gene dose, and the reduction is not due to changes in macroscopic or microscopic gating kinetics. The mechanism of abnormal membrane excitability in DM may in part be silencing of muscle Na channels due to Dmpk deficiency.
Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Sita
S
Reddy
Dilaawar J
DJ
Mistry
Qing Cai
QC
Wang
Lisa M
LM
Geddis
Howard C
HC
Kutchai
J Randall
JR
Moorman
J Paul
JP
Mounsey
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002469:Cell Separation; D004195:Disease Models, Animal; D018628:Gene Dosage; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000235:genetics; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D009223:Myotonic Dystrophy / Q000235:genetics / Q000378:metabolism*; D065636:Myotonin-Protein Kinase; D018408:Patch-Clamp Techniques; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency* / Q000235:genetics; D011869:Radioligand Assay; D012530:Saxitoxin / Q000493:pharmacokinetics; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*
C585516:DMPK protein, mouse; D015222:Sodium Channels; D012530:Saxitoxin; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases