Influence of temperature and external Ca2+ concentration upon dantrolene action on excitation-contraction coupling in frog skeletal muscle

Effects of dantrolene (DAN) on electrical and mechanical responses in frog skeletal muscle were studied at various Ca2+ concentrations and temperatures to elucidate the mechanism of action of DAN. The following results were obtained. (a) Twitch tension of a DAN-injected fiber, elicited by intracellular stimulation, increased transiently and then decreased whereas extracellular DAN always depressed the tension. (b) Lowering the external Ca2+ concentration resulted in the potentiation of twitch tension. The addition of DAN, however, reduced the tension significantly (p less than 0.05). (c) Extracellular DAN caused a transient reduction and subsequent elevation of the threshold current; however intracellular DAN caused only elevation of threshold. (d) DAN prevented the slow depolarization of the membrane in low Ca2+ medium. (e) These effects of the drug were temperature dependent, the effect being more pronounced at higher temperatures. These findings suggest that DAN may manifest its effects by replacement of Ca2+ from its binding sites on the membrane and that this occupation of the Ca2+ sites by DAN is temperature dependent.