EFFECTS OF BOLDINE ON MOUSE DIAPHRAGM AND SARCOPLASMIC-RETICULUM VESICLES ISOLATED FROM SKELETAL-MUSCLE

The effects of boldine [(S)-2,9-dihydroxy-1,10-dimethoxyaporphine], a major alkaloid in the leaves and bark of boldo (Peumus boldus Mel.), o n skeletal muscle were studied using mouse diaphragm and isolated sarc oplasmic reticulum membrane vesicles. Boldine, at 10-200 mu M, has lit tle effect on the muscle-evoked twitches; however, the ryanodine-induc ed contracture was potentiated dose-dependently. At higher concentrati ons of 300 mu M, boldine by itself induced muscle contracture of two p hases, which were caused by the influx of extracellular Ca2+ and induc tion of Ca2+ release from the internal Ca2+ storage site, the sarcopla smic reticulum, respectively. When tested with isolated sarcoplasmic r eticulum membrane vesicles, boldine dose-dependently induced Ca2+ rele ase from actively loaded sarcoplasmic reticulum vesicles isolated from skeletal muscle of rabbit or rat which was inhibited by ruthenium red , suggesting that the release was through the Ca2+ release channel, al so known as the ryanodine receptor, Boldine also dose-dependently incr eased apparent [H-3]-ryanodine binding with the EC50 value of 50 mu M. In conclusion, we have shown that boldine could sensitize the ryanodi ne receptor and induce Ca2+ release from the internal Ca2+ storage sit e of skeletal muscle.