Prolonged Inactivation of Nicotinic Acid Adenine Dinucleotide Phosphate-induced Ca2+ Release Mediates a Spatiotemporal Ca 2+ Memory

Abstract

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 Ca 2+ 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 ∼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.