Effects of age and gene dose on skeletal muscle sodium channel gating in mice deficient in myotonic dystrophy protein kinase

• Published in: Muscle & nerve Vol. 25; no. 6; pp. 850 - 857
• Main Authors: Reddy, Sita, Mistry, Dilaawar J., Wang, Qing Cai, Geddis, Lisa M., Kutchai, Howard C., Moorman, J. Randall, Mounsey, J. Paul
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 01.06.2002; Wiley
• Subjects: aging; Aging - metabolism; Animals; Cell Separation; Disease Models, Animal; Gene Dosage; In Vitro Techniques; Ion Channel Gating - drug effects; Ion Channel Gating - genetics; Kinetics; Maladies des muscles striés. Maladies neuromusculaires; Membrane Potentials - drug effects; Membrane Potentials - physiology; Mice; Mice, Inbred Strains; Mice, Knockout; Muscle, Skeletal - cytology; Muscle, Skeletal - metabolism; myotonic dystrophy; Myotonic Dystrophy - genetics; Myotonic Dystrophy - metabolism; myotonic dystrophy protein kinase; Myotonin-Protein Kinase; Neurologie; patch clamp; Patch-Clamp Techniques; Protein-Serine-Threonine Kinases - deficiency; Protein-Serine-Threonine Kinases - genetics; Radioligand Assay; saxitoxin; Saxitoxin - pharmacokinetics; Sciences biologiques et medicales; Sciences medicales; sodium channels; Sodium Channels - drug effects; Sodium Channels - metabolism; Myotonie; Enzyme; Transferases; Dystrophie myotonique; Neuromusculaire pathologie; Rodentia; Maladie héréditaire; Déficit; Dystrophie musculaire; Vertebrata; Mammalia; Canal ionique; Sodium; Protein kinase; Animal; Souris; Système nerveux pathologie; Excitabilité; Gène; Gating; Age; Muscle strié pathologie
• ISSN: 0148-639X; 1097-4598
• DOI: 10.1002/mus.10127

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. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000–000, 2002