IP3 receptor signaling and endothelial barrier function

The endothelium, a monolayer of endothelial cells lining vessel walls, maintains tissue-fluid homeostasis by restricting the passage of the plasma proteins and blood cells into the interstitium. The ion Ca2+, a ubiquitous secondary messenger, initiates signal transduction events in endothelial cells that is critical to control of vascular tone and endothelial permeability. The ion Ca2+ is stored inside the intracellular organelles and released into the cytosol in response to environmental cues. The inositol 1,4,5-trisphosphate (IP3) messenger facilitates Ca2+ release through IP3 receptors which are Ca2+-selective intracellular channels located within the membrane of the endoplasmic reticulum. Binding of IP3 to the IP3Rs initiates assembly of IP3R clusters, a key event responsible for amplification of Ca2+ signals in endothelial cells. This review discusses emerging concepts related to architecture and dynamics of IP3R clusters, and their specific role in propagation of Ca2+ signals in endothelial cells.