STIM1 Positively Regulates the Ca(2+) Release Activity of the Inositol 1,4,5-Trisphosphate Receptor in Bovine Aortic Endothelial Cells

The endothelium is actively involved in many functions of the cardiovascular system, such as the modulation of arterial pressure and the maintenance of blood flow. These functions require a great versatility of the intracellular Ca(2+) signaling that resides in the fact that different signals can be encoded by varying the frequency and the amplitude of the Ca(2+) response. Cells use both extracellular and intracellular Ca(2+) pools to modulate the intracellular Ca(2+) concentration. In non-excitable cells, the inositol 1,4,5-trisphosphate receptor (IP(3)R), located on the endoplasmic reticulum (ER), is responsible for the release of Ca(2+) from the intracellular store. The proteins STIM1 and STIM2 are also located on the ER and they are involved in the activation of a store-operated Ca(2+) entry (SOCE). Due to their Ca(2+) sensor property and their close proximity with IP(3)Rs on the ER, STIMs could modulate the activity of IP(3)R. In this study, we showed that STIM1 and STIM2 are expressed in bovine aortic endothelial cells and they both interact with IP(3)R. While STIM2 appears to play a minor role, STIM1 plays an important role in the regulation of agonist-induced Ca(2+) mobilization in BAECs by a positive effect on both the SOCE and the IP(3)R-dependent Ca(2+) release.