Fatigue-inducing stimulation resolves myotonia in a drug-induced model

Abstract

Background: Slowed muscle relaxation is the contractile hallmark of myotonia congenita, a disease caused by genetic CLC-1 chloride channel deficiency, which improves with antecedent brief contractions ("warm-up phenomenon"). It is unclear to what extent the myotonia continues to dissipate during continued repetitive contractions and how this relates temporally to muscle fatigue. Diaphragm, EDL, and soleus muscles were examined in vitro during repetitive 20 Hz and 50 Hz train stimulation in a drug-induced (9-AC) rat myotonia model.

Results: At the onset of stimulation, 9-AC treated diaphragm and EDL muscle had markedly prolonged half relaxation and late relaxation times (range 147 to 884 ms, 894 to 1324 ms). Half relaxation and late relaxation times reached near-normal values over the 5-10 and 10-40 subsequent contractions, respectively. In both muscles myotonia declined faster during repetitive 50 Hz than 20 Hz stimulation, and much faster than the rate of force loss during fatigue at both frequencies. Soleus muscle was resistant to the myotonic effects of 9-AC.

Conclusions: In a drug-induced model of mechanical myotonia, fatigue-inducing stimulation resolves the myotonia, which furthermore appears to be independent from the development of muscle fatigue.

Figure 1

Parameters measured for a diaphragm myotonic contraction at 20 Hz. The baseline is passive force related to stretching the muscle to optimal length, and all other active force values were quantified relative to baseline.

Figure 2

The effect of 9-AC on force production, contraction time, half relaxation time and late relaxation time in diaphragm muscle during repetitive 20 Hz and 50 Hz train stimulation. Contraction time was not measurable at 50 Hz. Values are means and bars indicate SD. P values are the results of analysis of variance; asterisks indicate significant differences found by the Newman-Keuls test in the event of significance by analysis of variance.

Figure 3

The effect of 9-AC on peak force, contraction time, half relaxation time, and late relaxation time in the soleus muscle during repetitive 20 Hz train stimulation. Values are means and bars indicate SD. P values are the results of analysis of variance; asterisks indicate significant differences found by the Newman-Keuls test in the event of significance by analysis of variance.

Figure 4

The effect of 9-AC on force production, contraction time, half relaxation time and late relaxation time in the EDL (extensor digitorum longus) muscle during repetitive 20 Hz and 50 Hz train stimulation. Values are means and bars indicate SD. P values are the results of analysis of variance; asterisks indicate significant differences found by the Newman-Keuls test in the event of significance by analysis of variance.