CYCLIC ADP-RIBOSE DOES NOT AFFECT CARDIAC OR SKELETAL-MUSCLE RYANODINE RECEPTORS

The cardiac muscle isoform of the ryanodine receptor/Ca2+ release channel (RYR) has been proposed to be an important target of cyclic ADP-ribose (cADPR) action in mammalian cells. However, we now demonstrate that neither cADPR (0.1-5 mu M), nor the related metabolites beta-NAD(+) (0.1-30 mM) and ADP-ribose (0.1-5 mu M), affected cardiac RYR activity as determined by [SH]ryanodine binding to cardiac sarcoplasmic reticulum (SR) vesicles. Similarly, cADPR (1 mu M) failed to activate single cardiac RYR channels in planar lipid bilayers. Skeletal muscle SR [H-3]ryanodine binding was also unaffected by cADPR (up to 30 mu M). These results argue against a direct role for the well-characterized RYRs of cardiac or skeletal muscle in mediating cADPR-activated Ca2+ release.