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. and Petersen, Ole Holger ORCID: https://orcid.org/0000-0002-6998-0380 2002. Transformation of local Ca2+ spikes to global Ca2+ transients: the combinatorial roles of multiple Ca2+ releasing messengers. EMBO Journal 21 (5) , pp. 909-919. 10.1093/emboj/21.5.909

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Systems Immunity Research Institute (SIURI)
Uncontrolled Keywords:	cyclic ADP‐ribose; inositol trisphosphate; local and global calcium; NAADP; pancreatic acinar cells
Publisher:	European Molecular Biology Organization
ISSN:	0261-4189
Last Modified:	27 Oct 2022 08:42
URI:	https://orca.cardiff.ac.uk/id/eprint/63159

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