NAADP induces Ca2+ oscillations via a two-pool mechanism by priming IP3- and cADPR-sensitive Ca2+ stores

In sea urchin eggs, Ca2+ mobilization by nicotinic acid adenine dinucleotid e phosphate (NAADP) potently self-inactivates but paradoxically induces lon g-term Ca2+ oscillations. We investigated whether NAADP-induced Ca2+ oscill ations arise from the recruitment of other Ca2+ release pathways. NAADP, in ositol trisphosphate (IP3) and cyclic ADP-ribose (cADPR) all mobilized Ca2 from internal stores but only NAADP consistently induced Ca2+ oscillations . NAADP-induced Ca2+ oscillations were partially inhibited by heparin or 8- amino-cADPR alone, but eliminated by the presence of both, indicating a req uirement for both IP3- and cADPR-dependent Ca2+ release. Thapsigargin compl etely blocked IP3 and cADPR responses as well as NAADP-induced Ca2+ oscilla tions, but only reduced the NAADP-mediated Ca2+ transient. Following NAADP- mediated release from this Ca2+ pool, the amount of CaZ+ in the Ca2+-induce d Ca2+ release stores was increased. These results support a mechanism in w hich CaZ+ oscillations are initiated by Ca2+ release from NAADP-sensitive C a2+ stores (pool 1) and perpetuated through cycles of Ca2+ uptake into and release from Ca2+-induced Ca2+ release stores (pool 2), These results provi de the first direct evidence in support of a two-pool model for Ca2+ oscill ations.