Functional role of TRPC channels in the regulation of endothelial permeability.
The endothelial cells (ECs) form a semipermeable barrier between the blood and the tissue. An important function of the endothelium is to maintain the integrity of the barrier function of the vessel wall. Ca(2+) signaling in ECs plays a key role in maintaining the barrier integrity. Transient receptor potential canonical (TRPC) channels are mammalian homologs of Drosophila TRP Ca(2+)-permeable channels expressed in EC. TRPC channels are thought to function as a Ca(2+) entry channel operated by store-depletion as well as receptor-activated channels in a variety of cell types, including ECs. Inflammatory mediators such as thrombin, histamine, bradykinin, and others increase endothelial permeability by actin polymerization-dependent EC rounding and formation of inter-endothelial gaps, a process critically dependent on the increase in EC cytosolic [Ca(2+)] ([Ca(2+)](i)). Increase in endothelial permeability depends on both intracellular Ca(2+) release and extracellular Ca(2+) entry through TRPC channels. This review summarizes recent findings on the role of TRPC channels in the mechanism of Ca(2+) entry in ECs, and, in particular, the role of TRPC channels in regulating endothelial barrier function.
Ahmmed
Gias U
GU
Department of Pharmacology and the Center for Lung and Vascular Biology, The University of Illinois, College of Medicine, 835 S Wolcott Avenue, Chicago, IL 60612, USA.
Malik
Asrar B
AB
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology*; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D011493:Protein Kinase C / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D050052:TRPC Cation Channels / Q000502:physiology*; D000074287:TRPC6 Cation Channel
D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; C489571:TRPC4 ion channel; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; C096351:transient receptor potential cation channel, subfamily C, member 1; D011493:Protein Kinase C; D002118:Calcium