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Spontaneous calcium release from inositol trisphosphate-sensitive calcium stores
L Missiaen1, C W Taylor, M J Berridge
1Department of Zoology, University of Cambridge, UK.
Nature
|July 18, 1991
Summary
Inositol 1,4,5-trisphosphate (InsP3) triggers calcium release from stores. Overloaded stores in hepatocytes spontaneously release calcium, a process influenced by InsP3 receptor sensitivity and promoting calcium oscillations.
Area of Science:
- Cellular Biology
- Biochemistry
- Physiology
Background:
- Inositol 1,4,5-trisphosphate (InsP3) is a key second messenger.
- InsP3 mobilizes calcium (Ca2+) from intracellular stores, like the endoplasmic reticulum.
- Ca2+ release by InsP3 exhibits all-or-none and quantal characteristics.
Purpose of the Study:
- To investigate the mechanism of InsP3-mediated Ca2+ release.
- To explore the role of intracellular Ca2+ concentration on InsP3 receptor sensitivity.
- To identify factors influencing spontaneous Ca2+ discharge from InsP3-sensitive stores.
Main Methods:
- Studied InsP3-sensitive calcium stores in isolated hepatocytes.
- Observed spontaneous Ca2+ discharge when stores were overloaded.
- Investigated the effect of heparin and sulfhydryl reagents (oxidized glutathione, thimerosal) on Ca2+ release and oscillations.
Main Results:
- InsP3-sensitive stores in hepatocytes spontaneously release Ca2+ when overloaded.
- This spontaneous release is inhibited by heparin.
- The process is preceded by increased InsP3 receptor sensitivity and promoted by specific sulfhydryl reagents, linking it to Ca2+ oscillations.
Conclusions:
- A novel mechanism for spontaneous Ca2+ release from InsP3-sensitive stores exists in hepatocytes.
- This process is regulated by Ca2+ levels and InsP3 receptor sensitivity.
- This mechanism may contribute to the generation of cellular Ca2+ oscillations and waves.