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

Journal article

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.

Authors: Churchill, G; Galione, A

• Publication status: Published
• Journal: EMBO journal
• Volume: 20
• Issue: 11
• Pages: 2666-2671
• Publication date: 2001-06-01
• DOI: 10.1093/emboj/20.11.2666
• EISSN: 1460-2075
• ISSN: 0261-4189
• Language: English
• Keywords: Calcium; Kinetics; Receptors, Cytoplasmic and Nuclear; Inositol 1,4,5-Trisphosphate; Oocytes; Adenosine Diphosphate Ribose; Calcium Channels; Sea Urchins; Calcium Signaling; Ryanodine Receptor Calcium Release Channel; Models, Biological; NADP; Thapsigargin; Oscillometry; Female; Animals; Cyclic ADP-Ribose; Inositol 1,4,5-Trisphosphate Receptors