Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholine / pharmacology
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Animals
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Caffeine / pharmacology
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Calcium / metabolism*
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Calcium / pharmacology
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Calcium Channels / drug effects
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Calcium Channels / physiology*
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Cells, Cultured
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Chloride Channels
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Cytoplasm / metabolism
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Heparin / pharmacology
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Inositol 1,4,5-Trisphosphate / metabolism*
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Inositol 1,4,5-Trisphosphate / pharmacology
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Ion Channels / drug effects
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Ion Channels / physiology
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Ionomycin / pharmacology
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Membrane Potentials / drug effects
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Membrane Proteins / physiology
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Mice
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Models, Biological
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Pancreas / drug effects
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Pancreas / metabolism*
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Receptors, Cholinergic / drug effects
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Receptors, Cholinergic / physiology*
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Signal Transduction
Substances
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Calcium Channels
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Chloride Channels
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Ion Channels
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Membrane Proteins
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Receptors, Cholinergic
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Caffeine
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Ionomycin
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Inositol 1,4,5-Trisphosphate
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Heparin
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Acetylcholine
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Calcium