INHIBITORS OF CA2+ RELEASE FROM THE ISOLATED SARCOPLASMIC-RETICULUM .1. CA2+ CHANNEL BLOCKERS

The effects of Ruthenium red and tetracaine, which inhibit Ca2+-induced Ca2+ release from the isolated [rabbit] sarcoplasmic reticulum on several types of Ca2+ release in vitro were investigated. Ca2+ release was triggered by several methods: addition of quercetin or caffeine, Ca2+ jump and replacement of potassium gluconate with choline chloride to produce membrane depolarization. The time-course of Ca2+ release was monitored using stopped-flow spectrophotometry and arsenazo III as a Ca2+ indicator. Ruthenium red inhibited all of these types of Ca2+ release with the same concentration for half-inhibition C1/2 = 0.08-0.10 .mu.M. Tetracaine inhibited these types of Ca2+ release with C1/2 = 0.07-0.11 mM. Procaine also inhibits both types of Ca2+ release induced by method 2 and 3 with C1/2 = 0.67-1.00 mM. Ruthenium red, tetracaine and procaine interfere with a common mechanism of the different types of Ca2+ release. Ruthenium red and tetracaine block the Ca2+ channel of sarcoplasmic reticulum.