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(Circulation. 1999;99:1719-1725.)
© 1999 American Heart Association, Inc.

Clinical Investigation and Reports

Hydrogen Peroxide, Potassium Currents, and Membrane Potential in Human Endothelial Cells

Rostislav Bychkov, PhD; Knud Pieper, MD; Christian Ried, PhD; Marianna Milosheva, PhD; Eugen Bychkov, PhD; Friedrich C. Luft, MD; Hermann Haller, MD

From the Franz Volhard Clinic and Max Delbrück Center for Molecular Medicine, Medical Faculty of the Charité, Humboldt University of Berlin, Berlin, Germany, and MREID Université du Littoral, Dunkerque, France (E.B.).

Correspondence to Hermann Haller, MD, Franz Volhard Clinic, Wiltberg Strasse 50, 13122 Berlin, Germany. E-mail haller{at}fvk-berlin.de

Background—Hydrogen peroxide (H₂O₂) and reactive oxygen species are implicated in inflammation, ischemia-reperfusion injury, and atherosclerosis. The role of ion channels has not been previously explored.

Methods and Results—K⁺ currents and membrane potential were recorded in endothelial cells by voltage- and current-clamp techniques. H₂O₂ elicited both hyperpolarization and depolarization of the membrane potential in a concentration-dependent manner. Low H₂O₂ concentrations (0.01 to 0.25 µmol/L) inhibited the inward-rectifying K⁺ current (K_IR). Whole-cell K⁺ current analysis revealed that H₂O₂ (1 mmol/L) applied to the bath solution increased the Ca²⁺-dependent K⁺ current (K_Ca) amplitude. H₂O₂ increased K_Ca current in outside-out patches in a Ca²⁺-free solution. When catalase (5000 µ/mL) was added to the bath solution, the outward-rectifying K⁺ current amplitude was restored. In contrast, superoxide dismutase (1000 u/mL) had only a small effect on the H₂O₂-induced K⁺ current changes. Next, we measured whole-cell K⁺ currents and redox potentials simultaneously with a novel redox potential-sensitive electrode. The H₂O₂-mediated K_Ca current increase was accompanied by a whole-cell redox potential decrease.

Conclusions—H₂O₂ elicited both hyperpolarization and depolarization of the membrane potential through 2 different mechanisms. Low H₂O₂ concentrations inhibited inward-rectifying K⁺ currents, whereas higher H₂O₂ concentrations increased the amplitude of the outward K⁺ current. We suggest that reactive oxygen species generated locally increases the K_Ca current amplitude, whereas low H₂O₂ concentrations inhibit K_IR via intracellular messengers.

Key Words: nitric oxide • potassium • free radicals • endothelium

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