Interaction of reactive oxygen species with ion transport mechanisms

Abstract

The use of electrophysiological and molecular biology techniques has shed light on reactive oxygen species (ROS)-induced impairment of surface and internal membranes that control cellular signaling. These deleterious effects of ROS are due to their interaction with various ion transport proteins underlying the transmembrane signal transduction, namely, 1) ion channels, such as Ca 2+channels (including voltage-sensitive L-type Ca 2+currents, dihydropyridine receptor voltage sensors, ryanodine receptor Ca 2+-release channels, andd- myo-inositol 1,4,5-trisphosphate receptor Ca 2+-release channels), K+channels (such as Ca 2+-activated K+channels, inward and outward K+currents, and ATP-sensitive K+channels), Na+channels, and Cl−channels; 2) ion pumps, such as sarcoplasmic reticulum and sarcolemmal Ca 2+pumps, Na+-K+-ATPase (Na+pump), and H+-ATPase (H+pump); 3) ion exchangers such as the Na+/Ca 2+exchanger and Na+/H+exchanger; and 4) ion cotransporters such as K+-Cl−, Na+-K+-Cl−, and P i-Na+cotransporters. The mechanism of ROS-induced modifications in ion transport pathways involves 1) oxidation of sulfhydryl groups located on the ion transport proteins, 2) peroxidation of membrane phospholipids, and 3) inhibition of membrane-bound regulatory enzymes and modification of the oxidative phosphorylation and ATP levels. Alterations in the ion transport mechanisms lead to changes in a second messenger system, primarily Ca 2+homeostasis, which further augment the abnormal electrical activity and distortion of signal transduction, causing cell dysfunction, which underlies pathological conditions.