Modulation of skeletal muscle sodium channels by human myotonin protein kinase

J. Paul Mounsey, Puting Xu, J. Edward John, L. Tyler Horne, John Gilbert, Allen D. Roses, J. Randall Moorman

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

In myotonic muscular dystrophy, abnormal muscle Na currents underlie myotonic discharges. Since the myotonic muscular dystrophy gene encodes a product, human myotonin protein kinase, with structural similarity to protein kinases, we tested the idea that human myotonin protein kinase modulates skeletal muscle Na channels. Coexpression of human myotonin protein kinase with rat skeletal muscle Na channels in Xenopus oocytes reduced the amplitude of Na currents and accelerated current decay. The effect required the presence of a potential phosphorylation site in the inactivation mechanism of the channel. The mutation responsible for human disease, trinucleotide repeats in the 3' untranslated region, did not prevent the effect The consequence of an abnormal amount of the kinase would be altered muscle cell excitability, consistent with the clinical finding of myotonia in myotonic dystrophy.

Original languageEnglish
Pages (from-to)2379-2384
Number of pages6
JournalJournal of Clinical Investigation
Volume95
Issue number5
StatePublished - May 1 1995
Externally publishedYes

Fingerprint

Sodium Channels
Myotonic Dystrophy
Skeletal Muscle
Muscular Dystrophies
Myotonia
Trinucleotide Repeats
3' Untranslated Regions
Xenopus
Protein Kinases
Muscle Cells
Oocytes
Phosphotransferases
Phosphorylation
Muscles
Mutation
Myotonin-Protein Kinase
Genes

Keywords

  • myotonic muscular dystrophy
  • phosphorylation
  • protein kinase
  • sodium channels

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Mounsey, J. P., Xu, P., John, J. E., Horne, L. T., Gilbert, J., Roses, A. D., & Moorman, J. R. (1995). Modulation of skeletal muscle sodium channels by human myotonin protein kinase. Journal of Clinical Investigation, 95(5), 2379-2384.

Modulation of skeletal muscle sodium channels by human myotonin protein kinase. / Mounsey, J. Paul; Xu, Puting; John, J. Edward; Horne, L. Tyler; Gilbert, John; Roses, Allen D.; Moorman, J. Randall.

In: Journal of Clinical Investigation, Vol. 95, No. 5, 01.05.1995, p. 2379-2384.

Research output: Contribution to journalArticle

Mounsey, JP, Xu, P, John, JE, Horne, LT, Gilbert, J, Roses, AD & Moorman, JR 1995, 'Modulation of skeletal muscle sodium channels by human myotonin protein kinase', Journal of Clinical Investigation, vol. 95, no. 5, pp. 2379-2384.
Mounsey JP, Xu P, John JE, Horne LT, Gilbert J, Roses AD et al. Modulation of skeletal muscle sodium channels by human myotonin protein kinase. Journal of Clinical Investigation. 1995 May 1;95(5):2379-2384.
Mounsey, J. Paul ; Xu, Puting ; John, J. Edward ; Horne, L. Tyler ; Gilbert, John ; Roses, Allen D. ; Moorman, J. Randall. / Modulation of skeletal muscle sodium channels by human myotonin protein kinase. In: Journal of Clinical Investigation. 1995 ; Vol. 95, No. 5. pp. 2379-2384.
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