Magnesium ions but not ATP inhibit cyclic ADP-ribose-induced calcium release

The pharmacology of the cyclic ADP-ribose (cADPR)-dependent Ca⁺² release mechanism is very similar to that of the ryanodine receptor (RyR). Here we showed that MgCl₂, a known inhibitor of RyR, blocked cADPR-induced Ca⁺² release in sea urchin egg homogenates with a half maximal concentration of about 2.5 mM. The effect was specific since up to 10 mM Mg⁺² had no effect on the Ca⁺² release induced by inositol trisphosphate. K₂ATP, another known modulator of RyR, at up to 10 mM did not affect the half-maximal concentration of cADPR, which remained at about 96 nM. These results indicate cADPR is a specific Ca⁺² release activator and not merely an adenine nucleotide acting on the ATP-site. The inhibitory effects of Mg⁺² further demonstrate the similarity between RyR and the cADPR-dependent Ca⁺² release system.