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Redox Control of Ion Channel Activity in Vascular Endothelial Cells by Glutathione
Author(s) -
Elliott Stephen J.,
Koliwad Suneil K.
Publication year - 1997
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.3109/10739689709146798
Subject(s) - glutathione , endoplasmic reticulum , chemistry , ion channel , vascular smooth muscle , intracellular , endothelial stem cell , biophysics , gating , nitric oxide , biochemistry , microbiology and biotechnology , inositol , signal transduction , ion transporter , stimulation , biology , receptor , endocrinology , in vitro , enzyme , membrane , organic chemistry , smooth muscle
ABSTRACT Oxidized glutathione (GSSG) is endogenously formed within vascular endothelial cells. The bioactivity of GSSG results in the oxidation of protein thiol groups, leading to changes in protein structure‐function relationships. When ion channel protein thiols are the target of oxidation by GSSG, important changes in channel conductance, activity, and gating occur. In this review, we focus on two endothelial cell ion channels, the activities of which influence vascular cell signaling and the nitric oxide signaling pathway. The first channel is the GSSG‐operated cation channel that depolarizes the endothelial cell, leading to inhibition of capacitative Ca 2+ entry. The second channel is the inositol 1,4,5‐triphosphate (IP 3 )‐operated Ca 2+ channel that is responsible for the agonist‐stimulated release of Ca 2+ from IP 3 ‐sensitive endoplasmic reticulum. GSSG acts to deplete IP 3 ‐sensitive Ca 2+ stores, thereby attenuating the intracellular Ca 2+ response to agonist stimulation. Together, these effects indicate that glutathione, which is formed endogenously within the cell, is a key physiological modulator of endothelial cell signaling.

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