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.
Repository Citation
Myers, J. H.,
Denman, K.,
DuPont, C.,
Hawash, A. A.,
Novak, K. R.,
Koesters, A.,
Grabner, M.,
Dayal, A.,
Voss, A. A.,
& Rich, M. M.
(2021). The Mechanism Underlying Transient Weakness in Myotonia Congenita. eLife, 10.
https://corescholar.libraries.wright.edu/ncbp/1184
DOI
10.7554/eLife.65691
Included in
Medical Cell Biology Commons, Medical Neurobiology Commons, Medical Physiology Commons, Neurosciences Commons, Physiological Processes Commons
Comments
This work is licensed under a Creative Commons Attribution 4.0 International License.