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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.

Original publication

DOI

10.1093/emboj/20.11.2666

Type

Journal article

Journal

EMBO J

Publication Date

01/06/2001

Volume

20

Pages

2666 - 2671

Keywords

Adenosine Diphosphate Ribose, Animals, Calcium, Calcium Channels, Calcium Signaling, Cyclic ADP-Ribose, Female, Inositol 1,4,5-Trisphosphate, Inositol 1,4,5-Trisphosphate Receptors, Kinetics, Models, Biological, NADP, Oocytes, Oscillometry, Receptors, Cytoplasmic and Nuclear, Ryanodine Receptor Calcium Release Channel, Sea Urchins, Thapsigargin