Cyclic ADP-ribose-gated Ca Release in Sea Urchin Eggs Requires an Elevated [Ca]*

Cyclic ADP-ribose (cADPr) has been shown to release intracellular Ca from sea urchin eggs and a variety of vertebrate cell types, although its mechanism of action remains elusive. We employed the caged version of cADPr to study the [Ca] transient kinetics in intact sea urchin eggs for insights into how cADPr gates Ca release. Ca release triggered by photolytic production of cADPr was initially slow, with an effective delay of several hundred milliseconds before the onset of a rapid Ca release phase. In contrast, Ca release induced by photolysis of caged inositol 1,4,5-trisphosphate was immediate in onset and roughly an order of magnitude faster. The delay before cADPr-induced Ca release was eliminated when the [Ca] was step-elevated coincident with the photoliberation of cADPr and greatly prolonged in the presence of exogenous Ca buffers. Thus, the slow onset of Ca release does not reflect an intrinsically slow rate by which cADPr gates release channels. Rather, a [Ca] rise from resting levels is needed to achieve more than minimal cADPr activity. Full release of Ca by cADPr in intact sea urchin eggs requires a positive Ca feedback.