Receptor-activated cytoplasmic Ca2+ spiking mediated by inositol trisphosphate is due to Ca2(+)-induced Ca2+ release.
Receptor-mediated inositol 1,4,5-trisphosphate (Ins-(1,4,5)P3) generation evokes fluctuations in the cytoplasmic Ca2+ concentration ([Ca2+]i). Intracellular Ca2+ infusion into single mouse pancreatic acinar cells mimicks the effect of external acetylcholine (ACh) or internal Ins(1,4,5)P3 application by evoking repetitive Ca2+ release monitored by Ca2(+)-activated Cl- current. Intracellular infusion of the Ins(1,4,5)P3 receptor antagonist heparin fails to inhibit Ca2+ spiking caused by Ca2+ infusion, but blocks ACh- and Ins(1,4,5)P3-evoked Ca2+ oscillations. Caffeine (1 mM), a potentiator of Ca2(+)-induced Ca2+ release, evokes Ca2+ spiking during subthreshold intracellular Ca2+ infusion. These results indicate that ACh-evoked Ca2+ oscillations are due to pulses of Ca2+ release through a caffeine-sensitive channel triggered by a small steady Ins(1,4,5)P3-evoked Ca2+ flow.
MRC Secretory Control Research Group, University of Liverpool, England.
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Wakui
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Osipchuk
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Petersen
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D018118:Chloride Channels; D003593:Cytoplasm / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism* / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D015759:Ionomycin / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction
D015220:Calcium Channels; D018118:Chloride Channels; D007473:Ion Channels; D008565:Membrane Proteins; D011950:Receptors, Cholinergic; D002110:Caffeine; D015759:Ionomycin; D015544:Inositol 1,4,5-Trisphosphate; D006493:Heparin; D000109:Acetylcholine; D002118:Calcium