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Hydrogen peroxide reduces Cx40, Cx43, and Cx45 gap junction function.

Yi X Li1, Donglin Bai2

  • 1Department of Physiology and Pharmacology, University of Western Ontario, London, ON, N6A 5C1, Canada.

Cell and Tissue Research
|February 16, 2026
PubMed
Summary

Hydrogen peroxide (H₂O₂), a reactive oxygen species (ROS), impairs cardiac gap junction (GJ) function. This reduction in GJ coupling and conductance may independently contribute to cardiac arrhythmias.

Keywords:
Cardiac arrhythmiasConnexinGap junction channelHydrogen peroxidePatch clampReactive oxygen species

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Area of Science:

  • Cardiovascular Biology
  • Cellular Electrophysiology
  • Oxidative Stress Research

Background:

  • Cardiac gap junctions (GJs), composed of connexins (Cx40, Cx43, Cx45), are vital for synchronized myocardial electrical activity.
  • Oxidative stress, marked by reactive oxygen species (ROS), is implicated in cardiac arrhythmias.
  • The precise mechanism by which ROS affects cardiac GJ function remains unclear.

Purpose of the Study:

  • To investigate the acute effects of hydrogen peroxide (H₂O₂), a key ROS, on cardiac GJ function.
  • To determine if H₂O₂ modulates GJ coupling probability, conductance, and channel gating.

Main Methods:

  • Utilized dual whole-cell patch clamp recordings in genetically engineered HEK293 cells expressing cardiac connexins (Cx40, Cx43, Cx45).
  • Assessed the impact of H₂O₂ application on GJ coupling parameters.

Main Results:

  • H₂O₂ significantly reduced GJ coupling probability and coupling conductance (Gj) for Cx45, Cx43, and Cx40.
  • Single channel conductance (γj) was significantly decreased for Cx40 and Cx43 GJs.
  • Transjunctional voltage-dependent gating (Vj-gating) of cardiac GJs was not affected by H₂O₂.

Conclusions:

  • Hydrogen peroxide acutely impairs cardiac GJ function by reducing coupling probability and conductance.
  • These H₂O₂-induced alterations in GJ function represent a potential independent mechanism promoting cardiac arrhythmias.