Interaction between store-operated and arachidonate-activated calcium entry

Holmes, Anthony M; Roderick, H. Llewelyn; McDonald, Fraser and Bootman, Martin D. (2007). Interaction between store-operated and arachidonate-activated calcium entry. Cell calcium, 41(1) pp. 1–12.



A ubiquitous pathway for cellular Ca2+ influx involves 'store-operated channels' that respond to depletion of intracellular Ca2+ pools via an as yet unknown mechanism. Due to its wide-spread expression, store-operated Ca2+ entry (SOCE) has been considered a principal route for Ca2+ influx. However, recent evidence has suggested that alternative pathways, activated for example by lipid metabolites, are responsible for physiological Ca2+ influx. It is not clear if these messenger-activated Ca2+ 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 Ca2+ 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 Ca2+ influx (denoted non-SOCE). Both Ca2+ entry routes could underlie substantial long-lasting Ca2+ 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 Ca2+ influx switched to the non-SOCE mechanism. Addition of arachidonate to naïve cells resulted in rapid activation of the non-SOCE pathway. However, this Ca2+ 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.

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