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  • The EMBO Journal (2002) 21, 909 - 919
  • doi:10.1093/emboj/21.5.909

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

Jose M. Cancela1, Fabien Van Coppenolle2, Antony Galione3, Alexei V. Tepikin4 and Ole H. Petersen4

  1. Laboratoire de Neurobiologie Cellulaire et Moléculaire, Unité CNRS UPR 9040, 1 Avenue de la terrasse, 91 198 Gif-sur-Yvette, France
  2. Laboratoire de Physiologie Cellulaire, INSERM EPI 9938, Université de Lille I, France
  3. Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK
  4. MRC Secretory Control Research Group, The Physiological Laboratory, University of Liverpool, Liverpool L69 3BX, UK

Correspondence to:

Jose M. Cancela, E-mail: jose.cancela@nbcm.cnrs-gif.fr

Received 29 October 2001; Accepted 10 January 2002; Revised 28 December 2001

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.

  • Keywords:

    • cyclic ADP-ribose,
    • inositol trisphosphate,
    • local and global calcium,
    • NAADP,
    • pancreatic acinar cells