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.

DOI: https://doi.org/10.1016/j.ceca.2006.04.005

Abstract

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.

Viewing alternatives

Metrics

Public Attention

Altmetrics from Altmetric

Number of Citations

Citations from Dimensions

Item Actions

Export

About

Recommendations