EFFECT OF DANTROLENE SODIUM ON THE INACTIVATION OF EXCITATION-CONTRACTION COUPLING IN FROG SKELETAL MUSCLE

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  • Effect of Dantrolene Sodium on the Inac

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The effect of dantrolene sodium on “inactivation 1 and 2”(see below) of potassium contracture in single fibers of frog semitendinosus muscle was studied. Dantrolene (2.5-10μM) clearly shortened the plateau duration and increased the rate of spontaneous relaxation of the contracture induced by 190mM K+, without appreciably affecting the peak tension; we tentatively termed these changes of contracture “inactivation 1.”On the other hand, in the presence of dantrolene at subthreshold K+ concentration, the time course of the inhibition of the peak contracture tension induced by 190mM K+ was markedly accelerated; we tentatively termed this inhibition “inactivation 2.” Similar results were obtained by dantrolene in the presence of some inactivationfacilitating factors, i. e., in the absence of Ca++ or at or low Ca++ concentrations, in the presence of 1-3mM procaine, or in the presence of both procaine and K+ in subthreshold concentrations (15 and 20mM). From these results, it is suggested that dantrolene has a marked facilitating effect on the mechanical inactivation (“inactivation 1”) which is considered to be related to spontaneous relaxation, whereas it has little effect on another type of inactivation (“inactivation 2”) related to the inhibition of peak tension which changes with time and that dantrolene has a potentiating effect on these two types of inactivations in the presence of the above inactivation-facilitating factors. It was also suggested that the sites of the mechanical inactivation in twitch muscle fibers may be localized at the transverse tubular membrane.

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