IP 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 Ca, a ubiquitous secondary messenger, initiates signal transduction events in endothelial cells that is critical to control of vascular tone and endothelial permeability. The ion Ca is stored inside the intracellular organelles and released into the cytosol in response to environmental cues. The inositol 1,4,5-trisphosphate (IP) messenger facilitates Ca release through IP receptors which are Ca-selective intracellular channels located within the membrane of the endoplasmic reticulum. Binding of IP to the IPRs initiates assembly of IPR clusters, a key event responsible for amplification of Ca signals in endothelial cells. This review discusses emerging concepts related to architecture and dynamics of IPR clusters, and their specific role in propagation of Ca signals in endothelial cells.