Interaction between store-operated and arachidonate-activated calcium entry.
A ubiquitous pathway for cellular Ca(2+) influx involves 'store-operated channels' that respond to depletion of intracellular Ca(2+) pools via an as yet unknown mechanism. Due to its wide-spread expression, store-operated Ca(2+) entry (SOCE) has been considered a principal route for Ca(2+) influx. However, recent evidence has suggested that alternative pathways, activated for example by lipid metabolites, are responsible for physiological Ca(2+) influx. It is not clear if these messenger-activated Ca(2+) entry routes exist in all cells and what interaction they have with SOCE. In the present study we demonstrate that HEK-293 cells and Saos-2 cells express an arachidonic acid (AA)-activated Ca(2+) influx pathway that is distinct from SOCE on the basis of sensitivity to pharmacological blockers and depletion of cellular cholesterol. We examined the functional interaction between SOCE and the arachidonate-triggered Ca(2+) influx (denoted non-SOCE). Both Ca(2+) entry routes could underlie substantial long-lasting Ca(2+) elevations. However, the two pathways could not operate simultaneously. With cells that had an on-going SOCE response, addition of arachidonate gave two profound effects. Firstly, it rapidly inhibited SOCE. Secondly, the mode of Ca(2+) influx switched to the non-SOCE mechanism. Addition of arachidonate to naïve cells resulted in rapid activation of the non-SOCE pathway. However, this Ca(2+) entry route was very slowly engaged if the SOCE pathway was already operative. These data indicate that the SOCE and arachidonate-activated non-SOCE pathways interact in an inhibitory manner. We probed the plausible mechanisms by which these two pathways may communicate.
Holmes
Anthony M
AM
The Babraham Institute, Laboratory of Molecular Signalling, Babraham, Cambridge CB2 4AT, UK.
Roderick
H Llewelyn
HL
McDonald
Fraser
F
Bootman
Martin D
MD
D000081:Acetamides / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
D000081:Acetamides; D015220:Calcium Channels; D007093:Imidazoles; D007546:Isoquinolines; C081356:LOE 908; D016718:Arachidonic Acid; D009569:Nitric Oxide; C031938:calmidazolium; D019284:Thapsigargin