Endothelial CRAC Channels

Store-operated Ca2+ entry (SOCE) is the primary Ca2+ entry mechanism in nonexcitable cells such as endothelial cells (ECs). When the endoplasmic reticulum (ER)-resident stromal-interacting molecules 1 and 2 (STIM1/2) sense the depletion of Ca2+ stores, they gain an extended conformation and move to interact with plasma membrane (PM) Orai channels within PM-ER junctions to trigger SOCE. Biophysically, SOCE is mediated by the Ca2+ release-activated Ca2+ (CRAC) current. SOCE was proposed to regulate many EC functions, including proliferation, migration, angiogenesis, and barrier permeability. Prior studies have provided evidence that dysregulation of endothelial SOCE underlies endothelial dysfunction in several vascular diseases. Here, we highlight the role of SOCE in regulating EC function and explore the potential of targeting Orai channels to treat vascular diseases.