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The Ca(2+)-mobilizing metabolite cyclic ADP-ribose (cADPR) has been shown to release Ca2+ from ryanodine-sensitive stores in many cells. We show that this metabolite at a concentration of 17 microM, but not its precursor beta-NAD+ nor non-cyclic ADPR at the same concentration, is active in releasing Ca2+ from rabbit skeletal muscle sarcoplasmic reticulum. The release was not sensitive to Ruthenium red (1 microM) nor to the ryanodine receptor-specific scorpion toxin Buthotus1-1 (10 microM). In planar bilayer single channel recordings, concentrations up to 50 microM cADPR did not increase the open probability of Ruthenium red and toxin-sensitive Ca2+ release channels. Thus Ca2+ release induced by cADPR in skeletal muscle sarcoplasmic reticulum may not involve opening of ryanodine receptors.
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