The effect of dantrolene on the enhancement and diminution of tension evoked by staircase and by tetanus in rat muscle

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Abstract
The effect of dantrolene on the potentiation of isometric twitch tension was examined during and after the staircase (5/s, 250 stimuli) and after the tetanus (167/s, 250 stimuli) in the extensor digitorum longus muscle of adult Lewis rats at 37-38.degree. C. The study confirmed that dantrolene decreased the twitch tension much more than the tetanic tension. The drug shortened the contraction time of the twitch. The rate of force development of the twitch was diminished by half that of the twitch tension. The drug shortened and diminished the activation of the muscle during the twitch. Dantrolene decreased the potentiation produced by a given number of stimuli early in the staircase. At the 250th stimulus the staircase was .apprx. 25% larger after than before application of the drug. Dantrolene increased the potentiation 2 s after the tetanus by .apprx. 60%. After application of dantrolene, the decay of potentiation after the staircase indicated that the process that diminished the twitch during the staircase, present before application of the drug, was absent. The size of the process causing potentiation was the same with and without the drug. Both events of potentiation after the tetanus were increased by dantrolene. Both after the staircase and after the tetanus, dantrolene increased the slow phase of decay by 60-70%. The fast rate of decay after the tetanus was unchanged by the drug. The contraction time was prolonged less in the potentiated twitch after than before application of dantrolene. This was presumably due to a greater relative increase in activation rather than to a prolongation of the time during which the muscle was activated. A model is proposed where the delay in potentiation during the staircase and the increase in potentiation after the tetanus are due to the proportion of sites in the excitation-contraction coupling occupied by dantrolene being reduced by repetitive depolarizations of the transverse tubules during trains of repetitive stimuli.