Tissue specificity: SOCE: Implications for Ca2+ handling in endothelial cells

Abstract

Many cellular functions of the vascular endothelium are regulated by fine-tuned global and local, microdomain-confined changes of cytosolic free Ca2+ ([Ca2+]i). Vasoactive agonist-induced stimulation of vascular endothelial cells (VECs) typically induces Ca2+ release through IP3 receptor Ca2+ release channels embedded in the membrane of the endoplasmic reticulum (ER) Ca2+ store, followed by Ca2+ entry from the extracellular space elicited by Ca2+ store depletion and referred to as capacitative or store-operated Ca2+ entry (SOCE). In vascular endothelial cells, SOCE is graded with the degree of store depletion and controlled locally in the subcellular microdomain where depletion occurs. SOCE provides distinct Ca2+ signals that selectively control specific endothelial functions: in calf pulmonary artery endothelial cells, the SOCE Ca2+ signal drives nitric oxide (an endothelium-derived relaxing factor of the vascular smooth muscle) production and controls activation and nuclear translocation of the transcription factor NFAT. Both cellular events are not affected by Ca2+ signals of comparable magnitude arising directly from Ca2+ release from intracellular stores, clearly indicating that SOCE regulates specific Ca2+-dependent cellular tasks by a unique and exclusive mechanism. This review discusses the mechanisms of intracellular Ca2+ regulation in vascular endothelial cells and the role of store-operated Ca2+ entry for endothelium-dependent smooth muscle relaxation and nitric oxide signaling, endothelial oxidative stress response, and excitation-transcription coupling in the vascular endothelium.