Luminal Ca2+ promoting spontaneous Ca2+ release from inositol trisphosphate-sensitive stores in rat hepatocytes

1. Spontaneous Ca2+ release from the inositol 1,4,5-trisphosphate (InsP3)-sensitive stores in permeabilized hepatocytes was monitored using Fluo-3 to measure the free [Ca2+] of the medium bathing the cells. 2. Permeabilized cells rapidly sequestered Ca2+, reducing the [Ca2+] to 103 +/- 5 nM. Under c...

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Bibliographic Details
Published in:The Journal of physiology 1992-09, Vol.455 (1), p.623-640
Main Authors: Missiaen, L, Taylor, C W, Berridge, M J
Format: Article
Language:English
Subjects:
Action Potentials - physiology
Animals
Biological and medical sciences
Caffeine - pharmacology
Calcium - metabolism
Cell Membrane Permeability
Fundamental and applied biological sciences. Psychology
Liver - cytology
Liver - metabolism
Mitochondria, Liver - metabolism
Rats
Rats, Wistar
Reaction Time
Stomach
Sulfhydryl Compounds - pharmacology
Vertebrates: digestive system
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Summary:1. Spontaneous Ca2+ release from the inositol 1,4,5-trisphosphate (InsP3)-sensitive stores in permeabilized hepatocytes was monitored using Fluo-3 to measure the free [Ca2+] of the medium bathing the cells. 2. Permeabilized cells rapidly sequestered Ca2+, reducing the [Ca2+] to 103 +/- 5 nM. Under conditions that depended critically upon cell density and the amount of Ca2+ in the medium, this was followed by a slow increase in [Ca2+] culminating in a substantial Ca2+ spike representing synchronous discharge from the InsP3-sensitive stores. 3. During the latency preceding the Ca2+ spike, the stores increased their sensitivity to InsP3. This sensitization seemed to be an all-or-none phenomenon. 4. Oxidized glutathione and thimerosal promoted the spontaneous release by sensitizing the InsP3 receptor. 5. An increase in the [Ca2+] within the stores was required for both the increased sensitivity to InsP3 and the subsequent spike. 6. Caffeine (6 mM) antagonized the effect of very low InsP3 concentrations and abolished the Ca2+ spike, without itself releasing Ca2+. 7. Our results suggesting that luminal Ca2+ may sensitive InsP3-sensitive stores leading to spontaneous Ca2+ mobilization will be discussed in the light of a modified version of the two-pool model for explaining cytosolic Ca2+ oscillations.
ISSN:0022-3751
1469-7793
DOI:10.1113/jphysiol.1992.sp019319