Transformation of local Ca² spikes to global Ca² transients: the combinatorial roles of multiple Ca² releasing messengers.

Cancela, Jose M.; van Coppenolle, Fabien; Galione, Antony; Tepikin, Alexei V.; Petersen, Ole H.

In pancreatic acinar cells, low, threshold concentrations of acetylcholine (ACh) or cholecystokinin (CCK) induce repetitive local cytosolic Ca2 spikes in the apical pole, while higher concentrations elicit global signals. We have investigated the process that transforms local Ca2 spikes to global Ca2 transients, focusing on the interactions of multiple intracellular messengers. ACh-elicited local Ca2 spikes were transformed into a global sustained Ca2 response by cyclic ADP-ribose (cADPR) or nicotinic acid adenine dinucleotide phosphate (NAADP), whereas inositol 1,4,5-trisphosphate (IP3) had a much weaker effect. In contrast, the response elicited by a low CCK concentration was strongly potentiated by IP3, whereas cADPR and NAADP had little effect. Experiments with messenger mixtures revealed a local interaction between IP3 and NAADP and a stronger global potentiating interaction between cADPR and NAADP. NAADP strongly amplified the local Ca2 release evoked by a cADPR/IP3 mixture eliciting a vigorous global Ca2 response. Different combinations of Ca2 releasing messengers can shape the spatio-temporal patterns of cytosolic Ca2 signals. NAADP and cADPR are emerging as key messengers in the globalization of Ca2 signals.

EXOCRINE glands; CALCIUM; CHOLECYSTOKININ; GASTROINTESTINAL hormones; ACETYLCHOLINE; CYTOSOL

EMBO Journal, 2002, Vol 21, Issue 5, p909

0261-4189

Academic Journal

10.1093/emboj/21.5.909