Transformation of local Ca2+ spikes to global Ca2+ transients: the combinatorial roles of multiple Ca2+ releasing messengers.
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.
Cancela
Jose M
JM
Laboratoire de Neurobiologie Cellulaire et Moléculaire, Unité CNRS UPR 9040, 1 Avenue de la terrasse, 91 198 Gif-sur-Yvette, France. jose.cancela@nbcm.cnrs-gif.fr
Van Coppenolle
Fabien
F
Galione
Antony
A
Tepikin
Alexei V
AV
Petersen
Ole H
OH
D000109:Acetylcholine / Q000494:pharmacology; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000502:physiology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D016764:Cell Polarity; D002766:Cholecystokinin / Q000494:pharmacology; D036563:Cyclic ADP-Ribose; D005089:Exocytosis / Q000187:drug effects; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology / Q000502:physiology*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D051379:Mice; D009249:NADP / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D010179:Pancreas / Q000166:cytology; D018408:Patch-Clamp Techniques; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000502:physiology; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology*; D012844:Sincalide / Q000494:pharmacology
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D011956:Receptors, Cell Surface; D011949:Receptors, Cholecystokinin; D011950:Receptors, Cholinergic; D018160:Receptors, Cytoplasmic and Nuclear; C067025:cyclic ADP-ribose receptor; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D002110:Caffeine; D009249:NADP; C024376:NAADP; D015544:Inositol 1,4,5-Trisphosphate; D002766:Cholecystokinin; D012844:Sincalide; D000109:Acetylcholine