REDOX CONTROL OF ION-CHANNEL ACTIVITY IN VASCULAR ENDOTHELIAL-CELLS BY GLUTATHIONE

Oxidized glutathione (GSSG) is endogenously formed within vascular end othelial cells. The bioactivity of GSSG results in the oxidation of pr otein thiol groups, leading to changes in protein structure-function r elationships. When ion channel protein thiols are the target of oxidat ion by GSSG, important changes in channel conductance, activity, and g ating occur. In this review, we focus on two endothelial cell ion chan nels, the activities of which influence vascular cell signaling and th e nitric oxide signaling pathway. The first channel is the GSSG-operat ed cation channel that depolarizes the endothelial cell, leading to in hibition of capacitative Ca2+ entry. The second channel is the inosito l 1,4,5-triphosphate (IP3)-operated Ca2+ channel that is responsible f or the agonist-stimulated release of Ca2+ from IP3-sensitive endoplasm ic reticulum. GSSG acts to deplete IP3-sensitive Ca2+ stores, thereby attenuating the intracellular Ca2+ response to agonist stimulation. To gether, these effects indicate that glutathione, which is formed endog enously within the cell, is a key physiological modulator of endotheli al cell signaling.