Hydrogen peroxide, potassium currents, and membrane potential in human endothelial cells

Area of Science:

• Endothelial cell physiology
• Cardiovascular research
• Oxidative stress signaling

Background:

• Reactive oxygen species, including hydrogen peroxide (H2O2), are linked to inflammation, ischemia-reperfusion injury, and atherosclerosis.
• The specific role of ion channels in H2O2-mediated cellular responses remains largely unexplored.

Purpose of the Study:

• To investigate the effects of hydrogen peroxide (H2O2) on ion channel function and membrane potential in endothelial cells.
• To elucidate the mechanisms by which H2O2 influences potassium (K+) currents and cellular electrophysiology.

Main Methods:

• Utilized voltage- and current-clamp techniques to record K+ currents and membrane potential in endothelial cells.
• Applied varying concentrations of H2O2 and measured changes in inward-rectifying K+ (KIR) and Ca2+-dependent K+ (KCa) currents.
• Employed catalase and superoxide dismutase to differentiate H2O2 effects and measured redox potentials simultaneously with K+ currents.

Main Results:

• H2O2 induced both hyperpolarization and depolarization of the endothelial cell membrane in a concentration-dependent manner.
• Low H2O2 concentrations (0.01–0.25 µmol/L) inhibited KIR, while higher concentrations (1 mmol/L) increased KCa current amplitude.
• H2O2-induced KCa current increase correlated with a decrease in whole-cell redox potential, suggesting a direct redox-sensitive mechanism.

Conclusions:

• H2O2 modulates endothelial cell membrane potential via distinct mechanisms involving K+ channels.
• Low H2O2 concentrations inhibit KIR, likely through intracellular messengers.
• Higher H2O2 concentrations enhance KCa current amplitude, potentially through locally generated reactive oxygen species impacting redox state.