Inhibitory effect of dicumarol on the excitability of the sarcolemma of skeletal muscle.
Dicumarol (7.5 x 10(-6) M -7.5 x 10(-5) M) inhibited the twitches and the simultaneously recorded electromyogram of the indirectly stimulated rat diaphragm preparation. The directly stimulated curarized preparation was inhibited in a similar way. Accordingly, the excitability of the sarcolemma was inhibited by dicumarol. The inhibitory effect was irreversible upon washing. Intracellular microelectrode recordings disclosed that the inhibitory effect was accompanied by a depolarization, and the inhibition was potentiated in high K+ (9.5 mM) solution. In addition, the ability of the preparations to produce a depolarization contracture with KCl (100 mM) was inhibited by dicumarol. Therefore, a part of the inhibitory effect might be caused by the depolarization. On the other hand, subthreshold direct stimulation disclosed that the inhibitory effect might be due to an increase of the threshold. However, a lack of synergistic interaction with lidocaine (0.2 mM) showed that this effect of dicumarol was probably not a membrane stabilizing or local anaesthetic effect.
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Department of Physiology and Biochemistry, Dental Faculty, University of Oslo, Norway.
D000779:Anesthetics, Local; D000818:Animals; D001728:Dicumarol / Q000494:pharmacology*; D004357:Drug Synergism; D004576:Electromyography / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009132:Muscles / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012508:Sarcolemma / Q000187:drug effects*
D000779:Anesthetics, Local; D001728:Dicumarol; D008012:Lidocaine