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 dinucleotide phosphate (NAADP) potently self‐inactivates but paradoxically induces long‐term Ca2+ oscillations. We investigated whether NAADP‐induced Ca2+ oscillations arise from the recruitment of other Ca2+ release pathways. NAADP, inositol 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 requirement for both IP3‐ and cADPR‐dependent Ca2+ release. Thapsigargin completely blocked IP3 and cADPR responses as well as NAADP‐induced Ca2+ oscillations, but only reduced the NAADP‐mediated Ca2+ transient. Following NAADP‐mediated release from this Ca2+ pool, the amount of Ca2+ in the Ca2+‐induced Ca2+ release stores was increased. These results support a mechanism in which Ca2+ oscillations are initiated by Ca2+ release from NAADP‐sensitive Ca2+ stores (pool 1) and perpetuated through cycles of Ca2+ uptake into and release from Ca2+‐induced Ca2+ release stores (pool 2). These results provide the first direct evidence in support of a two‐pool model for Ca2+ oscillations.

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