The effect of dehydroepiandrosterone sulfate (DHEAS) on myotonia: intracellular studies.
OBJECTIVE
In order to find some appropriate medicine to suppress myotonia without decreasing muscle strength experiments were performed on myotonic (mto) mice whose Cl channel does not develop due to stop codon and serves as an animal model of myotonia. In myotonic dystrophy dehydroepiandrosterone is low in the serum and it has been reported that intravenous injections of DHEAS to human cases improves myotonia and activities of daily living.


METHODS
Three pairs of heterozygote mto mice, SWR/J-Clcn1(adr-mto/+) and ten Wistar rats were used. We performed intracellular recordings of myotonia from mto mice and the drug effects on insertion myotonia were recorded from the hemidiaphragm preparations of mto mice with different concentrations of DHEAS. Isometric twitch tension was recorded from rat hemidiaphragm preparations in Tyrode's solution and the effect of DHEAS on the muscle twitch tension was measured at different concentrations of DHEAS from 100 mg/l to 300 mg/l. The effect of mexiletine on ITT was also measured.


RESULTS
In mto mice insertion myotonia was recorded as soon as the microelectrode was inserted in the muscle cells. When DHEAS was added to Tyrode's solution, insertion myotonia was suppressed. DHEAS decreased ITT up to 70% of the original value, though mexiletine decreased ITT to 30% of the original value. Therefore, the decrement of the muscle strength in DHEAS solution is much smaller than that of mexiletine.


CONCLUSIONS
Since myotonic dystrophy shows progressive muscle weakness in addition to myotonia, medications like DHEAS are more favorable than the typical Na channel blocker.
Nakazora
Hiroshi
H
Division of Neurology, Department of Internal Medicine, Toho University Ohashi Medical Center, Tokyo, Japan.
Kurihara
Teruyuki
T
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D019314:Dehydroepiandrosterone Sulfate / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004594:Electrophysiology / Q000379:methods; D007537:Isometric Contraction / Q000187:drug effects*; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D009222:Myotonia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D019314:Dehydroepiandrosterone Sulfate