Effects Of Camkii Regulation On Atrial Action Potential Under Oxidative Stress Condition

Previous studies have demonstrated that oxidative stress is closely associated with cardiac arrhythmias via altering electrical activity and intracellular calcium dynamics of cardiac myocytes. The present study developed a human atrial cell model including effects of oxidative stress by incorporating reactive oxygen species (ROS)-induced CaMKII activation and its downstream effects on different ionic channels. The CaMKII dynamics was mimicked by a novel 6-state Markov chain model, including both autophosphorylation and oxidation pathways of CaMKII activation. Simulation results show that highly activated CaMKII by massive ROS phosphorylated L-type Ca2+ current (I-CaL) and elevated intracellular calcium concentration, which eventually resulted in calcium overload in sarcoplasmic reticulum in the condition of oxidative stress. Meanwhile, calcium overload resulted in increase of calcium release and cytoplasmic calcium concentration, which triggered afterdepolarizations (DADs) by increasing the calcium extrusion via the Na+-Ca2+ exchanger (NCX) current. This study revealed effects of massive ROS on calcium cycling in atrial myocytes and shed lights on mechanisms of cardiac arrhythmias induced by oxidative stress.