Differential susceptibility of muscles to myotonia and force impairment in a mouse model of myotonic dystrophy.

ABSTRACT

INTRODUCTION: Myotonic dystrophy, or dystrophia myotonica (DM), is characterized by prominent muscle wasting and weakness as well as delayed muscle relaxation resulting from persistent electrical discharges. METHODS: We hypothesized heterogeneity among muscles in degree of weakness and myotonia in an expanded [(CUG)(250)] repeats transgenic (HSA(LR)) mouse DM model. Muscle contraction was compared among diaphragm, extensor digitorum longus (EDL), and soleus muscles. RESULTS: Myotonia was found only in EDL, as manifested by longer late-relaxation time and elevated myotonic index. EDL, but not the other two muscles, had impaired force over a wide range of stimulation frequencies. During fatigue-inducing stimulation, DM EDL muscle force per cross-sectional area was significantly impaired during 25-Hz stimulation, whereas there were no differences in fatigue response for DM diaphragm or soleus. CONCLUSION: In an expanded repeats model of DM the EDL is more susceptible to myotonia and force impairment than muscles with lower proportions of fast-twitch fibers.