H2O2 activates redox- and 4-aminopyridine-sensitive Kv channels in coronary vascular smooth muscle

Paul A. Rogers, William M. Chilian, Ian N. Bratz, Robert M. Bryan, Gregory M. Dick

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

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 H 2O2 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). H 2O2 increased a conductance that was half-activated at -18 ± 1 mV and half-inactivated at -36 ± 2 mV. H2O 2 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 H 2O2 to increase K+ current. Neither tetraethylammonium (1 mM) nor iberiotoxin (100 nM), antagonists of Ca 2+-activated K+ channels, blocked the effect of H 2O2 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 H 2O2 increases the activity of 4-AP-sensitive KV channels. Furthermore, our data support the idea that 4-AP-sensitive K V channels are redox sensitive and contribute to H2O 2-induced coronary vasodilation.

Original languageEnglish
Pages (from-to)H1404-H1411
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number3
DOIs
StatePublished - 1 Mar 2007

Keywords

  • Coronary circulation
  • Delayed-rectifier potassium channels
  • Peroxides
  • Reactive oxygen species
  • Sulfhydryl compounds

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