Treatment of myotonia congenita with retigabine in mice.

In this study, we found that retigabine greatly reduced the duration of myotonia in vitro. Detailed study of its mechanism of action revealed that retigabine had no effect on any of the traditional measures of muscle excitability such as resting potential, input resistance or the properties of single action potentials. Instead it appears to shorten myotonia by activating K+ current during trains of action potentials. Retigabine also greatly reduced the severity of myotonia in vivo, which was measured using a muscle force transducer. Despite its efficacy in vivo, retigabine did not improve motor performance of mice with myotonia congenita. There are a number of potential explanations for the lack of motor improvement in vivo including central nervous system side effects. Nonetheless, the striking effectiveness of retigabine on muscle itself suggests that activating potassium currents is an effective method to treat disorders of muscle hyperexcitability.
PMID: 30738808 [PubMed - as supplied by publisher]

Source: Experimental Neurology - February 7, 2019 Category: Neurology Authors: Dupont CX, Denman KS, Hawash AA, Voss AA, Rich MM Tags: Exp Neurol Source Type: research