Review Article
Cellular and Molecular Mechanisms of Arrhythmia by Oxidative Stress
Table 1
A summary of mechanisms of oxidative stress induced arrhythmia and potential therapeutic targets.
| Affected ion channels | Na+ current reduction (via PKC and c-Src, also via abnormal splicing) ⇒ reduction in conduction velocity | KATP inhibition ⇒ repolarization abnormality | NCX activation ⇒ increasing inward current and facilitating afterdepolarization | , , inhibition ⇒ abnormal repolarization | Increase in inward Ca++ current (direct or via CaMKII activation) ⇒ facilitating afterdepolarization | Increase in late Na+ current ⇒ facilitating afterdepolarization |
| Effect on intracellular Ca++ handling | Impairment of SERCA ⇒ increase intracellular Ca++ levels ⇒ facilitating afterdepolarization | Affecting RyR receptor (via CaMKII activation) ⇒ leakiness of SR ⇒ increase intracellular Ca++ levels ⇒ facilitating afterdepolarization |
| Effect on myocyte-myocyte coupling | Affecting assembling of Cx43 at gap junctions ⇒ reduction in conduction velocity |
| Effect on extracellular matrix | Activating fibrotic process (via TGF-) ⇒ reduction in conduction velocity and impaired myocyte-myocyte coupling due to collagen deposition |
|
|
CaMKII: Ca2+/calmodulin-dependent protein kinases II; Cx43: connexin 43; NCX: Na+/Ca2+ exchanger; RyR: ryanodine receptor; SERCA: sarco-/endoplasmic reticulum Ca++ - ATPase; TGF-β: Transforming Growth Factor-β.
|