IP3 receptor signaling and endothelial barrier function

Abstract

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 critical for 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 IP3Rs clusters, a key event responsible for amplification of Ca2+ signals in endothelial cells. This review discusses emerging concepts related to architecture and dynamics of IP3Rs clusters, and their specific role in propagation of Ca2+ signals in endothelial cells.

Endothelial Ca2+ Signaling, Angiogenesis and Vasculogenesis: Just What It Takes to Make a Blood Vessel

“…InsP 3 evokes endogenous Ca 2+ release by binding to the non-selective cation channels, InsP 3 R [18,83,84], which are located in the ER membrane (Figure 1). The resulting opening of InsP 3 R leads to the efflux of intraluminal Ca 2+ along the electrochemical gradient between the ER and the cytosol, where [Ca 2+ ] i quickly raises from around 100 nM up to 1 μM [18,83]. InsP 3 R modulate a wealth of processes, including proliferation, migration, gene expression, fluid secretion, synaptic plasticity, contraction, and membrane excitability [85].…”

“…InsP 3 R modulate a wealth of processes, including proliferation, migration, gene expression, fluid secretion, synaptic plasticity, contraction, and membrane excitability [85]. Three InsP 3 R isoforms, i.e., InsP 3 R1-3, have been described in mammalian cells [86], all of which are present throughout vascular endothelium [18], although their pattern of expression may vary depending on the species and the vascular bed [81,83,87,88,89,90,91]. We refer the readers to a recent review, which provides a comprehensive overview of endothelial InsP 3 R [83].…”

Endothelial TRPV4 channels modulate vascular tone by Ca2+‐induced Ca2+ release at inositol 1,4,5‐trisphosphate receptors

“…et al, 2019). Ca 2+ release via IP 3 R occurs in response to physical forces and circulating vasoactive substances and contributes to the control of several vascular activities such as vasorelaxation, endothelial permeability, and production of anti-thrombotic factors (Sun, Geyer, & Komarova, 2017 (Berridge, 1997;Bootman, Niggli, Berridge, & Lipp, 1997). These waves may move through all or part of the cell .…”

“…Ca 2+ release from the internal store in endothelial cells may be mediated mainly by IP 3 Rs (Mumtaz et al, ; Wilson et al, ). Ca 2+ release via IP 3 R occurs in response to physical forces and circulating vasoactive substances and contributes to the control of several vascular activities such as vasorelaxation, endothelial permeability, and production of anti‐thrombotic factors (Sun, Geyer, & Komarova, ).…”

High expression of type I inositol 1,4,5-trisphosphate receptor in the kidney of rats with hepatorenal syndrome

“…Therefore, IP 3 Rs mediates an important Ca 2+ signaling pathway in the cell, and the expression of IP 3 Rs is closely related to the sensitivity of the kidney to vasoconstrictors[ 33 - 35 ]. IP 3 Rs has four types of ligand binding sites associated with calcium channels[ 36 - 39 ], and renal IP 3 RI is mainly found in GMCs and VSMCs, and there is almost no IP 3 RI on the surface of other renal cells[ 40 , 41 ]. Therefore, the expression levels of IP 3 RI in renal GMCs and VSMCs may be related to renal vasoconstriction.…”