Cellular and Molecular Mechanisms of Arrhythmia by Oxidative Stress

Figure 1

Schematic review of some of the important known mechanisms by which excess ROS may induce arrhythmia. Activation of CaMKII, c-Src, and PKC may mediate several important effects of ROS on ionic currents resulting in arrhythmia. In addition, ROS adversely affect splicing of mRNA of cardiac sodium channels resulting in abnormal truncated cardiac sodium channel proteins and a reduction in normal sodium channels. ROS also increase fibrosis and impair gap junction conduction, resulting in reduced myocyte coupling. Abnormal splicing, activation of CaMKII, c-Src, and PKC are among emerging new antiarrhythmic therapeutic targets. CaMKII: Ca²⁺/calmodulin-dependent protein kinases II; CX43: connexin 43; NCX: Na⁺/Ca²⁺ exchanger; PLB: phospholamban; ROS: reactive oxygen species; RYR: ryanodine receptor; SERCA: sarco-/endoplasmic reticulum Ca²⁺-ATPase; TGF-β: Transforming Growth Factor-β; ZO-1: Zonula Occludens-1.