Drug-induced myotonia in human intercostal muscle.
The myotonia-inducing effects of furosemide and clofibrate, two widely used pharmaceutical agents, were investigated in excised human external intercostal muscle. The effects of anthracene-9-carboxylic acid (9-AC), a well-known myotonia-producing chemical, were also tested for comparison. In the presence of these drugs the electrical threshold was lowered, and a constant current pulse produced multiple spiking. Short trains of direct stimuli were often followed by after-activity, and this caused a myotonia-like prolongation of muscle contraction. Voltage-clamp experiments showed that 0.05 mM anthracene-9-carboxylic acid, 1 mM furosemide, and 1 mM clofibrate decreased the chloride conductance of the muscle fiber membrane to 14, 18, and 40%, respectively, of the normal value, and the myotonia-inducing potency of the 3 drugs was correlated with the decreased chloride conductance. The potassium currents were not affected by these compounds.
Kwieciński
H
H
Neurologische Klinik and Poliklinik der Technischen Universität Müchen, Federal Republic of Germany.
Lehmann-Horn
F
F
Rüdel
R
R
D000873:Anthracenes / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D002994:Clofibrate / Q000494:pharmacology*; D005665:Furosemide / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007366:Intercostal Muscles / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects*; D009222:Myotonia / Q000139:chemically induced*
D000873:Anthracenes; D002712:Chlorides; D007473:Ion Channels; C010030:9-anthroic acid; D005665:Furosemide; D002994:Clofibrate