BEE VENOM MELITTIN IS A POTENT TOXIN FOR REDUCING THE THRESHOLD FOR CALCIUM-INDUCED CALCIUM RELEASE IN HUMAN AND EQUINE SKELETAL-MUSCLE

The Modulation of Ca2+ release by synthetic bee venom melittin was examined in equine and human terminal cisternae-containing fractions. Melittin (0.1 muM) decreased the threshold of Ca2+-induced Ca2+ release by 20% in equine muscle and by 36% in human muscle. If terminal cisternae fractions were first preloaded with Ca2+ to greater than about 75% of the threshold of Ca2+-induced Ca2+ release and then melittin added, an immediate and sustained release of Ca2+ occurred in preparations from both species. Addition of melittin after a Ca2+ preload of < 50% of the threshold of Ca2+-induced Ca2+ release did not elicit sustained Ca2+ release. Ruthenium red (10 muM) antagonized all effects of melittin on Ca2+ release. Melittin (0.1-10 muM) did not affect [H-3]ryanodine binding. Melittin (0.1 muM) slightly (10%) inhibited the Ca2+ pump and this action was not antagonized by ruthenium red. These findings suggest that melittin may be an important new probe of the Ca2+-modulated Ca2+ release process that does not act at the ryanodine binding site.