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An inositol 1,4,5-trisphosphate-sensitive Ca2+ pool in liver nuclei
P Nicotera1, S Orrenius, T Nilsson
1Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
Summary
Rat liver nuclei actively manage calcium (Ca2+) levels, sequestering and buffering it. Inositol trisphosphate (Ins(1,4,5)P3) triggers Ca2+ release from a specific nuclear pool, impacting cellular signaling.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Recent studies identified an ATP- and calmodulin-dependent Ca2+ uptake system in rat liver nuclei.
- This system influences free Ca2+ concentration within the nuclear matrix.
Purpose of the Study:
- To investigate the capacity of liver nuclei to sequester and buffer Ca2+.
- To determine the role of the nucleus in regulating cytosolic free Ca2+ concentration.
- To examine the effect of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] on nuclear Ca2+ levels.
Main Methods:
- Investigated Ca2+ sequestration and buffering by isolated rat liver nuclei.
- Utilized Ins(1,4,5)P3 to stimulate Ca2+ release from nuclei.
- Analyzed Ca2+ reuptake into nuclear compartments.
Main Results:
- Liver nuclei exhibit significant Ca2+ sequestration and buffering capabilities.
- Ins(1,4,5)P3 stimulates the release of a portion of nuclear Ca2+.
- A transient decrease in intranuclear free Ca2+ concentration follows Ins(1,4,5)P3 stimulation.
- Ca2+ is subsequently reuptaken into an Ins(1,4,5)P3-insensitive nuclear compartment.
- Demonstrated the existence of at least two distinct Ca2+ pools within liver nuclei.
Conclusions:
- Liver nuclei play a role in regulating cytosolic free Ca2+ concentration.
- Ins(1,4,5)P3 releases Ca2+ from a specific nuclear pool, indicating nuclear Ca2+ signaling.
- These findings support a role for the nucleus in modulating cytosolic Ca2+ levels in response to agonists.
- Nuclear Ca2+ regulation by second messengers may influence hormone-mediated intranuclear processes.