Dantrolene blocks the tonic contraction and calcium influx evoked by K+ in ileal longitudinal smooth muscle

1. Dantrolene (10(-5)-10(-4) M) reduced the K+ (60 mM) tonic response in accordance with decreased Ca2+ uptake, as determined by La method, more than the phasic in ileal muscle. 2. After saponin-treatment of the fibers, which leaves the Ca2+ storage sites intact, dantrolene had only a slight effect on the caffeine-induced contraction. In Triton-X-100-treated fibers, in which the Ca2+ release sites are destroyed, dantrolene did not affect the Ca(2+)-induced contraction. 3. The results suggest that dantrolene inhibited the high-K(+)-induced tonic response mainly by inhibiting Ca2+ influx via voltage-dependent Ca2+ channels in ileum without affecting contractile elements. In contrast, dantrolene had only a slight effect on the intracellular Ca2+ release from caffeine-sensitive release sites.