Effects of disulfiram on excitation-contraction coupling in rat soleus muscle.
The aim of this study was to analyze whether disulfiram could affect excitation-contraction coupling in rat slow-twitch ( soleus) muscle.In small bundles of intact fibers, the amplitude and the time constant of relaxation of twitch and potassium contractures were dose-dependently and reversibly reduced by disulfiram at concentrations up to 27 microM. At larger concentrations (up to 67.5 microM) these effects were still present but less pronounced. In the presence of disulfiram (27 microM), the relationship between the amplitude of potassium contractures and membrane potential was shifted to more positive potentials whereas, the steady state inactivation curve was unchanged. These observations suggest that disulfiram has no effect on voltage sensors. In saponin-skinned fibers, the amount of Ca(2+) taken up, estimated by using the amplitude of 10 mM of caffeine contracture, was increased by disulfiram (27 microM). By contrast no significant modification was observed in the sensitivity of the ryanodine receptors to caffeine (contractures generated at 5 mM of caffeine) and in the myofibrillar Ca(2+) sensitivity (Triton X-100 skinned fibers). These results indicate that disulfiram induces a dose-dependent reversible effect on the contractile responses of soleus mammalian skeletal muscle by acting mainly on the sarcoplasmic reticulum Ca(2+)-ATPase activity.
D000427:Alcohol Deterrents / Q000494:pharmacology*; D000465:Algorithms; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003285:Contractile Proteins / Q000378:metabolism; D004221:Disulfiram / Q000494:pharmacology*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000502:physiology; D018657:Muscle Fibers, Slow-Twitch / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology
D000427:Alcohol Deterrents; D003285:Contractile Proteins; D010726:Phosphodiesterase Inhibitors; D002110:Caffeine; D000252:Calcium-Transporting ATPases; D002118:Calcium; D004221:Disulfiram