Hydrogen peroxide reduces Cx40, Cx43, and Cx45 gap junction function
摘要
Cardiac gap junctions (GJs), formed by connexin 40 (Cx40), Cx43, and Cx45, are essential for the rapid propagation of action potentials in the myocardium, which synchronizes the atria and ventricles to produce a rhythmic heartbeat. Oxidative stress is characterized by elevated levels of reactive oxygen species (ROS) and is a known contributor to cardiac arrhythmias. However, it is not clear whether the proarrhythmic action of ROS is linked to its modulation of cardiac GJs among other membrane channels. Here, we investigated the acute effects of hydrogen peroxide (H₂O₂), an ROS, on the function of cardiac GJs expressed in genetically engineered human embryonic kidney (HEK293) cells with dual whole-cell patch clamp recordings. We found that H₂O₂ significantly reduced the probability of cell pairs showing GJ coupling and the coupling conductance (Gj) for Cx45, Cx43, and Cx40 GJs. Single channel conductance (γj) for both Cx40 and Cx43 GJs was found to be significantly reduced, while the transjunctional voltage-dependent gating (Vj-gating) of all cardiac GJs remained unaffected. Our data demonstrate that one of the key ROS (H2O2) could reduce cardiac GJ function, which could be an independent factor to promote cardiac arrhythmias.