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Am J Physiol Heart Circ Physiol 292: H1404-H1411, 2007. First published October 27, 2006; doi:10.1152/ajpheart.00696.2006
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H2O2 activates redox- and 4-aminopyridine-sensitive Kv channels in coronary vascular smooth muscle

Paul A. Rogers,1 William M. Chilian,1 Ian N. Bratz,2 Robert M. Bryan, Jr.,3 and Gregory M. Dick2

1Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana; and 2Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana; and 3Department of Anesthesiology, Baylor College of Medicine, Houston, Texas

Submitted 30 June 2006 ; accepted in final form 25 October 2006

Previously, we demonstrated that coronary vasodilation in response to hydrogen peroxide (H2O2) is attenuated by 4-aminopyridine (4-AP), an inhibitor of voltage-gated K+ (KV) channels. Using whole cell patch-clamp techniques, we tested the hypothesis that H2O2 increases K+ current in coronary artery smooth muscle cells. H2O2 increased K+ current in a concentration-dependent manner (increases of 14 ± 3 and 43 ± 4% at 0 mV with 1 and 10 mM H2O2, respectively). H2O2 increased a conductance that was half-activated at –18 ± 1 mV and half-inactivated at –36 ± 2 mV. H2O2 increased current amplitude; however, the voltages of half activation and inactivation were not altered. Dithiothreitol, a thiol reductant, reversed the effect of H2O2 on K+ current and significantly shifted the voltage of half-activation to –10 ± 1 mV. N-ethylmaleimide, a thiol-alkylating agent, blocked the effect of H2O2 to increase K+ current. Neither tetraethylammonium (1 mM) nor iberiotoxin (100 nM), antagonists of Ca2+-activated K+ channels, blocked the effect of H2O2 to increase K+ current. In contrast, 3 mM 4-AP completely blocked the effect of H2O2 to increase K+ current. These findings lead us to conclude that H2O2 increases the activity of 4-AP-sensitive KV channels. Furthermore, our data support the idea that 4-AP-sensitive KV channels are redox sensitive and contribute to H2O2-induced coronary vasodilation.

reactive oxygen species; peroxides; sulfhydryl compounds; delayed-rectifier potassium channels; coronary circulation



Address for reprint requests and other correspondence: G. M. Dick, Dept. of Cellular and Integrative Physiology, Indiana Univ. School of Medicine, 635 Barnhill Dr., MS 385, Indianapolis, IN 46202-5120 (e-mail: gdick{at}iupui.edu)




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