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Interaction between store-operated and arachidonate-activated calcium entry.
Anthony M Holmes1, H Llewelyn Roderick, Fraser McDonald
1The Babraham Institute, Laboratory of Molecular Signalling, Babraham, Cambridge CB2 4AT, UK.
Cell Calcium
|June 13, 2006
Summary
Cellular calcium (Ca2+) influx occurs via store-operated Ca2+ entry (SOCE) and arachidonic acid (AA)-activated pathways. These distinct pathways interact, with AA inhibiting SOCE and switching influx to the non-SOCE mechanism.
Area of Science:
- Cell Biology
- Physiology
- Biochemistry
Background:
- Store-operated Ca2+ entry (SOCE) is a primary mechanism for cellular Ca2+ influx following depletion of intracellular Ca2+ stores.
- Emerging evidence suggests alternative Ca2+ influx pathways, activated by lipid metabolites, may also play significant physiological roles.
- The existence and interaction of these alternative pathways with SOCE remain largely uncharacterized.
Purpose of the Study:
- To investigate the presence and characteristics of an arachidonic acid (AA)-activated Ca2+ influx pathway in HEK-293 and Saos-2 cells.
- To determine the functional relationship and potential interactions between SOCE and the AA-activated non-SOCE pathway.
- To explore the underlying mechanisms governing the communication between these two Ca2+ influx pathways.
Main Methods:
- Utilized pharmacological blockers and cellular cholesterol depletion to differentiate between SOCE and AA-activated Ca2+ influx.
- Examined the functional interplay between SOCE and AA-activated non-SOCE by monitoring Ca2+ influx under various conditions.
- Assessed the impact of arachidonic acid on ongoing SOCE and the activation kinetics of the non-SOCE pathway.
Main Results:
- Demonstrated the existence of a distinct AA-activated Ca2+ influx pathway (non-SOCE) in HEK-293 and Saos-2 cells, separate from SOCE.
- Showed that SOCE and non-SOCE pathways cannot operate simultaneously, indicating a functional interaction.
- Observed that arachidonic acid rapidly inhibits SOCE and switches Ca2+ influx to the non-SOCE mechanism, while non-SOCE activation is slow if SOCE is already active.
Conclusions:
- The study identifies and characterizes an arachidonic acid-activated Ca2+ influx pathway that is functionally distinct from SOCE.
- Established an inhibitory interaction between SOCE and the AA-activated non-SOCE pathway, suggesting a regulatory crosstalk.
- These findings provide insights into the complex regulation of cellular Ca2+ homeostasis by distinct influx mechanisms.