INDUCTION OF CALCIUM-RELEASE FROM SARCOPLASMIC-RETICULUM OF SKELETAL-MUSCLE BY XANTHONE AND NORATHYRIOL

1 Effects of xanthone and its derivative, 1,3,6,7-tetrahydroxyxanthone (norathyriol), on Ca2+ release and ryanodine binding were studied in isolated sarcoplasmic reticulum (SR) vesicles from rabbit skeletal mus cle. 2 Both xanthone and norathyriol dose-dependently induced Ca2+ rel ease from the actively loaded SR vesicles which was blocked by rutheni um red, a specific Ca2+ release inhibitor, and Mg2+. 3 Xanthone and no rathyriol also dose-dependently increased apparent [H-3]-ryanodine bin ding. Norathyriol, but not xanthone, produced a synergistic effect on binding activation when added concurrently with caffeine. 4 In the pre sence of Mg2+, which inhibits ryanodine binding, both caffeine and nor athyriol, but not xanthone, could restore the binding to the level obs erved in the absence of Mg2+. 5 Xanthone activated the Ca2+-ATPase act ivity of isolated SR vesicles dose-dependently reaching 70% activation at 300 mu M. 6 When tested in mouse diaphragm, norathyriol potentiate d the muscle contraction followed by twitch depression and contracture in either a Ca2+-free bathing solution or one containing 2.5 mM Ca2+. These norathyriol-induced effects on muscle were inhibited by pretrea tment with ruthenium red or ryanodine. 7 These data suggest that xanth one and norathyriol can induce Ca2+ release from the SR of skeletal mu scle through a direct interaction with the Ca2+ release channel, also known as the ryanodine receptor.