EFFECTS OF BIPYRIDYLIUM COMPOUNDS ON CALCIUM-RELEASE FROM TRIADIC VESICLES ISOLATED FROM RABBIT SKELETAL-MUSCLE

1 The effects of 1,1 '-diheptyl-4,4'-bipyridinium dibromide (DHBP), a viologen for electrochromic memory display agent, on calcium release a nd ryanodine binding were studied with triad-rich sarcoplasmic reticul um (SR) vesicles isolated from rabbit skeletal muscle. 2 DHBP inhibite d the calcium release induced by 2 mM caffeine and 2 mu g ml(-1) polyl ysine with an IC50 value of 5 mu g ml(-1) and 4 mu g ml(-1) respective ly. 3 DHBP inhibited [H-3]-ryanodine binding in a dose-dependent manne r with an IC50 of 2.5 mu g ml(-1) and 90-100% inhibition at 20-30 mu g ml(-1). 4 Calcium uptake by SR was inhibited in the presence of caffe ine and this inhibition was antagonized by concomitant addition of DHB P. 5 The effect of DHBP on muscle twitches was studied on the mouse di aphragm. Muscle twitches elicited by direct electrical muscle stimulat ion and contractions induced by either 10 mM caffeine or 1 mu M ryanod ine were blocked by pretreatment with DHBP. 6 Data from this study pro vided evidence that DHBP blocked the calcium release from SR by direct interaction with the calcium release channel, also known as the ryano dine receptor. A possible use of this agent as a specific inhibitor fo r calcium release and as a muscle relaxant was suggested.