Abstract
1. The effects of 1,1'-diheptyl-4,4'-bipyridinium dibromide (DHBP), a viologen for electrochromic memory display agent, on calcium release and ryanodine binding were studied with triad-rich sarcoplasmic reticulum (SR) vesicles isolated from rabbit skeletal muscle. 2. DHBP inhibited the calcium release induced by 2 mM caffeine and 2 micrograms ml-1 polylysine with an IC50 value of 5 micrograms ml-1 and 4 micrograms ml-1 respectively. 3. DHBP inhibited [3H]-ryanodine binding in a dose-dependent manner with an IC50 of 2.5 micrograms ml-1 and 90-100% inhibition at 20-30 micrograms ml-1. 4. Calcium uptake by SR was inhibited in the presence of caffeine and this inhibition was antagonized by concomitant addition of DHBP. 5. The effect of DHBP on muscle twitches was studied on the mouse diaphragm. Muscle twitches elicited by direct electrical muscle stimulation and contractions induced by either 10 mM caffeine or 1 microM ryanodine were blocked by pretreatment with DHBP. 6. Data from this study provided evidence that DHBP blocked the calcium release from SR by direct interaction with the calcium release channel, also known as the ryanodine receptor. A possible use of this agent as a specific inhibitor for calcium release and as a muscle relaxant was suggested.
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