TRP Channels and the Regulation of Vascular Permeability

Abstract

See related article, pages 988–995 One of the most widely recognized mechanisms to initiate an inflammatory response is calcium entry into endothelial cells.1–3 Recent investigations have demonstrated that there are multiple mechanisms which determine calcium flux into endothelial cells (including ligand gated calcium channels, store operated calcium channels and mechanosensitive channels), and that these different mechanisms are preferentially distributed between different endothelial cells. The functional consequences of these observations for regulation of vascular tone and remodeling are beginning to be understood4,5 but this is not the case for the regulation of endothelial barrier function in intact organs. In this issue Alvarez et al describe an important example of segmental vascular permeability regulation in lung.6 They demonstrate that activation of the vanilloid subset of the family of calcium channels known as transient receptor potential channels (in this case the TRPV4 channels) preferentially increased the permeability of the endothelial and epithelial layers of the primary gas exchanging septal regions of the lung microvasculature whereas other calcium channels, such as the store operated calcium channels, increased permeability outside the primary gas exchange regions (so called extra-alveolar regions). These are important observations because disruption of the endothelium at the septal barrier is more likely to cause alveolar flooding and impair gas exchange than disruption in extra-alveolar vessels. So far at least 28 mammalian TRP isoforms have been discovered. TRP channels have been subdivided into 3 main classes, TRPC (canonical), TRPM (melastatin), and TRPV (vanilloid) although more recently other classes have also been proposed (TRPP [polycystin], TRPML [mucolipin], and TRPA [ankyrin]).4,7 A general feature of the channels is that they pass only very small currents (calcium ion flux) and act as passive conductance pathways for calcium entry, ie, they are not voltage gated. Thus the calcium flux depends on the …