Cyclic ADP-ribose-gated Ca2+ release in sea urchin eggs requires an elevated [Ca2+]

Cyclic ADP-ribose (cADPr) has been shown to release intracellular Ca2+ 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 [Ca2+] transient kinetics in intact sea urchin eggs for insights into how cADPr gates Ca2+ release. Ca2+ release triggered by photolytic production of cADPr was initially slow, with an effective delay of several hundred milliseconds before the onset of a rapid. Ca2+ release phase, in contrast, Ca2+ 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 Ca2+ release was eliminated when the [Ca2+] was step-elevated coincident with the photoliberation of cADPr and greatly prolonged in the presence of exogenous Ca2+ buffers. Thus, the slow onset of Ca2+ release does not reflect an intrinsically slow rate by which cADPr gates release channels, Rather, a [Ca2+] rise from resting levels is needed to achieve more than minimal cADPr activity, Fun release of Ca2+ by cADPr in intact sea urchin eggs requires a positive Ca2+ feedback.