Oxidative stress and potassium channel function

1. Modulation of K+ channel activities by cellular oxidative stress has emerged as a significant determinant of vasomotor function in multiple disease states. 2. Evidence from in vitro and in vivo studies suggest that superoxide (O-2(-)) and hydrogen peroxide (H2O2) enhance BKCa channel activity in rat and cat cerebral arterioles; however, activity is decreased by peroxynitrite (ONOO- ) in rat cerebral arteries. The mechanisms of changes in BKCa channel properties are not fully understood and may involve oxidation of cysteine residues that are located in the cell membranes. 3. Studies further suggest that O-2(-) increases K-ATP channel activity in guinea-pig cardiac myocytes, but decreases opening in cerebral vasculature. Both H2O2 and ONOO- enhance K-ATP channel activity in the myocardium and in coronary, renal, mesenteric and cerebral vascular beds. Alteration of K-ATP channels by free radicals may be due to oxidation of SH groups or changes in the cytosolic concentration of ATP. 4. It does appear that O-2(-) produced by either reaction of xanthine and xanthine oxidase or elevated levels of glucose reduces K-v channel activity and the impairments can be partially restored by free radical scavengers, superoxide dismutase and catalase. 5. Thus, redox modulation of potassium channel activity is an important mechanism regulating cell vascular smooth muscle membrane potential.