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

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 (G_j) for Cx45, Cx43, and Cx40.
• Single channel conductance (γ_j) was significantly decreased for Cx40 and Cx43 GJs.
• Transjunctional voltage-dependent gating (V_j-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.