title: Firewall function of the endothelial glycocalyx in the regulation of sodium homeostasis.
abstract: Plasma sodium, slightly above normal and in presence of aldosterone, stiffens vascular endothelium and reduces nitric oxide release with the consequence of endothelial dysfunction. This process is mediated by epithelial sodium channels (ENaC) and, most likely, the endothelial Na(+)/K(+)-ATPase. Both, ENaC and Na(+)/K(+)-ATPase, are located in the plasma membrane of endothelial cells and embedded in the endothelial glycocalyx (eGC). This negatively charged biopolymer is directly exposed to the blood stream and selectively buffers sodium ions. We hypothesize that the glycocalyx could interfere with endothelial sodium transport when extracellular sodium varies in the physiological range. Therefore, we modeled the endothelial cell as a pump-leak system measuring changes of intracellular sodium in cultured human endothelial cells. Experiments were performed under low/high extracellular sodium conditions before and after enzymatic eGC removal, and with inhibition of Na(+)/K(+)-ATPase and ENaC, respectively. Three major observations were made: (1) eGC removal by heparinase treatment facilitates sodium to enter/exit the endothelial cells. (2) The direction of net sodium movement across the endothelial plasma membrane depends on the concentration of extracellular sodium which regulates both the Na(+)/K(+)-ATPase and ENaC activity. (3) Removal of eGC and inhibition of sodium transport modify the electrical resistance of endothelial cells. We conclude that the eGC serves as a potential "firewall" preventing uncontrolled access of sodium to the pump-leak system of the endothelial cell. After eGC removal, sodium access to the system is facilitated. Thus the pump-leak system could be regulated by ambient sodium and control vascular permeability in pathophysiological conditions.
authors: Institute of Physiology II, University of Muenster, Robert-Koch-Strasse 27 b, 48149, Münster, Germany.
authors: Stefanie
authors: S
authors: Korte
authors: Anne
authors: A
authors: Wiesinger
authors: Alexandra S
authors: AS
authors: Straeter
authors: Wladimir
authors: W
authors: Peters
authors: Hans
authors: H
authors: Oberleithner
authors: Kristina
authors: K
authors: Kusche-Vihrog
mesh_terms: D001692:Biological Transport / Q000502:physiology; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D053503:Epithelial Sodium Channels / Q000502:physiology; D019276:Glycocalyx / Q000187:drug effects / Q000502:physiology*; D019763:Heparin Lyase / Q000494:pharmacology; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology
chemical_list: D053503:Epithelial Sodium Channels; D012964:Sodium; D019763:Heparin Lyase; D000254:Sodium-Potassium-Exchanging ATPase