Prolonged inactivation of nicotinic acid adenine dinucleotide phosphate-induced Ca2+ release mediates a spatiotemporal Ca2+ memory

Although numerous extracellular stimuli are coupled to increases in intracellular Ca2+, different stimuli are thought to achieve specificity by eliciting different spatiotemporal Ca2+ increases. We investigated the effect of nicotinic acid adenine dinucleotide phosphate (NAADP) inactivation on spatiotemporal Ca2+ signals in intact sea urchin eggs. The photorelease of NAADP but not inositol 1,4,5-trisphosphate or cyclic ADP-ribose resulted in self-inactivation. When NAADP was released first locally and subsequently globally, the spatial pattern of the first response shaped that of the second. Specifically, the local release of NAADP created a Ca2+ gradient that was reversed during the subsequent global release of NAADP. Neither cyclic ADP-ribose nor inositol 1,4,5-trisphosphate showed a similar effect. In contrast to homogenates, NAADP inactivation was reversible in intact eggs with resensitization occurring in similar to 20 min. Because initial NAADP responses affect later responses, NAADP can serve as a mechanism for a Ca2+ memory that has both spatial and temporal components. This NAADP-mediated Ca2+ memory provides a novel mechanism for cells to control spatiotemporal Ca2+ increases.