Inhibitors of Ca 2+ release from the isolated sarcoplasmic reticulum. I. Ca 2+ channel blockers

Abstract

The effects of Ruthenium red and tetracaine, which inhibit Ca 2+-induced Ca 2+ release from the isolated sarcoplasmic reticulum (e.g., Ohnishi, S.T. (1979) J. Biochem. (Tokyo) 86, 1147–1150), on several types of Ca 2+ release in vitro were investigated. Ca 2+ release was triggered by several methods: (1) addition of quercetin or caffeine, (2) Ca 2+ jump, and (3) replacement of potassium gluconate with choline chloride to produce membrane depolarization. The time-course of Ca 2+ release was monitored using stopped-flow spectrophotometry and arsenazo III as a Ca 2+ indicator. Ruthenium red inhibited all of these types of Ca 2+ release with the same concentration for half-inhibition C 1 2 = 0.08-0.10 μ M . Similarly, tetracaine inhibited these types of Ca 2+ release with C 1 2 = 0.07−0.11 mM . Procaine also inhibits both types of Ca 2+ release induced by method 2 and 3 with C 1 2 = 0.67−1.00 mM . These results suggest that Ruthenium red, tetracaine and procaine interfere with a common mechanism of the different types of Ca 2+ release. On the basis of several pieces of evidence we propose that Ruthenium red and tetracaine block the Ca 2+ channel of sarcoplasmic reticulum.