Complex role of STIM1 in the activation of store-independent Orai1/3 channels

• DOI: 10.1085/jgp.201311084
• Publication Date: 2014-02-24T16:58:37Z
• Authors: Xuexin Zhang; Wei Zhang; José C. González-...; Isaac Jardin; Christoph Romanin; Khalid Matrougui; Mohamed Trebak
• Keywords: Orai1; HEK 293 cells

Orai proteins contribute to Ca(2+) entry into cells through both store-dependent, release-activated (CRAC) channels (Orai1) and store-independent, arachidonic acid (AA)-regulated (ARC) leukotriene C4 (LTC4)-regulated (LRC) (Orai1/3 heteromultimers). Although activated by fundamentally different mechanisms, CRAC channels, like ARC LRC require stromal interacting molecule 1 (STIM1). The role of endoplasmic reticulum-resident STIM1 (ER-STIM1) in channel activation is widely accepted. ER-STIM1 necessary sufficient for vascular smooth muscle (VSMCs), the minor pool located at plasma membrane (PM-STIM1) HEK293 cells. To determine whether conductances are mediated same or populations STIM1, Orai1, Orai3 proteins, we used whole-cell perforated patch-clamp recording compare AA- LTC4-activated currents VSMCs We found that cell types show indistinguishable nonadditive LTC4- AA-activated Orai1 Orai3, suggesting channel. Experiments using a nonmetabolizable form AA an inhibitor 5-lipooxygenase suggested could be either LTC4 AA, with being more potent. PM-STIM1 was required current under recordings types, patch recordings. These results demonstrate cellular suggest complex regulating these store-independent Orai1/3 channels.