Excitation-contraction uncoupling in the rat diaphragm by 2,3-butanedione monoxime.
2,3-Butanedione monoxime (BDM), 0.5-12.5 mM, inhibited the twitches rapidly and reversibly in the rat diaphragm. A more extensive inhibition at direct than at indirect stimulation, a simultaneous effect on the electromyogram, and an attenuation of the inhibitory effect in preparations made hyperexcitable with Ca(2+)-free solution, myotonia or veratridine, indicated an interference with the gating mechanism of the sarcolemma. The excitation-contraction uncoupling with BDM was additive to the similar effect of dantrolene. A synergistic effect was not found, and neither agent alone nor both in combination caused a complete excitation-contraction uncoupling. Several differences between the effects of BDM and dantrolene were disclosed: Lowering the temperature increased and decreased the effect of BDM and dantrolene, respectively. Tetanic stimulation and high Ca2+ or high K+ antagonized the effect of dantrolene and did not affect the BDM-induced inhibition. Ca(2+)-free solution potentiated the effect of dantrolene and antagonized the effect of BDM. Caffeine and KCl contractures were inhibited by BDM, whereas the propranolol contracture due to Na,K-ATPase inhibition, which is completely inhibited by dantrolene, was unaffected by BDM.
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Department of Oral Biology, Dental Faculty, University of Oslo, Blindern, Norway.
D000818:Animals; D002118:Calcium / Q000502:physiology; D003620:Dantrolene / Q000494:pharmacology; D003931:Diacetyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D003964:Diaphragm / Q000187:drug effects / Q000294:innervation; D004357:Drug Synergism; D004576:Electromyography; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000187:drug effects; D011188:Potassium / Q000502:physiology; D051381:Rats
C004717:diacetylmonoxime; D003620:Dantrolene; D003931:Diacetyl; D011188:Potassium; D002118:Calcium