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The Mechanism Underlying Transient Weakness in Myotonia Congenita
eLife
  • Jessica H Myers, Wright State University
  • Kirsten Denman
  • Chris DuPont
  • Ahmed A Hawash
  • Kevin R Novak
  • Andrew Koesters
  • Manfred Grabner
  • Anamika Dayal
  • Andrew A Voss, Wright State University - Main Campus
  • Mark M Rich, Wright State University - Main Campus
Document Type
Article
Publication Date
4-27-2021
Identifier/URL
92866956 (Orcid)
Abstract

In addition to the hallmark muscle stiffness, patients with recessive myotonia congenita (Becker disease) experience debilitating bouts of transient weakness that remain poorly understood despite years of study. We performed intracellular recordings from muscle of both genetic and pharmacologic mouse models of Becker disease to identify the mechanism underlying transient weakness. Our recordings reveal transient depolarizations (plateau potentials) of the membrane potential to -25 to -35 mV in the genetic and pharmacologic models of Becker disease. Both Na + and Ca 2+ currents contribute to plateau potentials. Na + persistent inward current (NaPIC) through Na V 1.4 channels is the key trigger of plateau potentials and current through Ca V 1.1 Ca 2+ channels contributes to the duration of the plateau. Inhibiting NaPIC with ranolazine prevents the development of plateau potentials and eliminates transient weakness in vivo. These data suggest that targeting NaPIC may be an effective treatment to prevent transient weakness in myotonia congenita.

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Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
DOI
10.7554/eLife.65691
Citation Information
Jessica H Myers, Kirsten Denman, Chris DuPont, Ahmed A Hawash, et al.. "The Mechanism Underlying Transient Weakness in Myotonia Congenita" eLife Vol. 10 (2021) ISSN: 2050-084X
Available at: http://works.bepress.com/mark_rich/99/