Abstract
BackgroundSlowed 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.ResultsAt 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.ConclusionsIn 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.
Highlights
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”)
Muscle from humans and animals with myotonia congenita has physiological, structural and biochemical alterations which transcend the loss of CLC-1 channels, including hypertrophy or atrophy, alterations in fiber type composition, and altered amounts of parvalbumin [1,5,7,9,11,12,13,17,18]
In order to avoid the effects of downstream structural and biochemical changes resulting from genetic CLC-1 channel deficiency that can affect muscle fatigue properties in manners apart from the myotonia itself, the present study utilized Cl- channel blockade with 9-anthracene carboxylic acid (9-AC) to produce myotonia in otherwise normal muscle rather than testing muscle that is genetically deficient in Clchannels
Summary
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”). In order to avoid the effects of downstream structural and biochemical changes (eg., alterations in fiber type composition and atrophy or hypertrophy [1,5,7,9,11,12,13,17,18]) resulting from genetic CLC-1 channel deficiency that can affect muscle fatigue properties in manners apart from the myotonia itself, the present study utilized Cl- channel blockade with 9-AC to produce myotonia in otherwise normal muscle rather than testing muscle that is genetically deficient in Clchannels. Muscles pertinent to breathing (diaphragm), fast twitch movements (EDL), and slow twitch movements (soleus) were tested to determine whether 9-AC has varying effects on muscles with different fiber type compositions
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