Role of CaMKII in CaMKII/[Na+]i/[Ca2+]i Feedback in Myocardial Ischemia and Reperfusion Injury: A Simulation Study

Citation: Yu J, Zhang M, Qi J. Role of CaMKII in CaMKII/[Na+]i/[Ca2+]i Feedback in Myocardial Ischemia and Reperfusion Injury: A Simulation Study. Interv Cardiol J 2015, 2:1. Myocardial ischemia and reperfusion injury (MIRI) is a serious complication after percutaneous coronary intervention, which leads to heart failure, increased infarction size, and severe arrhythmias [1,2]. Various signaling pathways were found to be participated in the process of MIRI, such as phosphatidylinositol 3-kinase (PI3K)/AKT, extracellular signal-regulated kinase (ERK), endothelial NO synthase (eNOS), etc[3-5]. Recently, more and more studies demonstrate that Na+/Ca2+/Calmodulin-dependent protein kinase II (CaMII) feedback plays vital role in heart failure [6]. Over-activity of CaMKII enhanced the late Na+ current(INaL), caused intracellular Na+ ([Na]i) increasing, changing the equilibrium of the Na+-Ca2+ exchanger (NCX) to impair forwardmode (Ca2+ extrusion), and aggravating reverse-mode (Ca2+ influx) exchange. Subsequently, this Ca2+ overload further activate CaMKII and cause a feedback loop of CaMKII/[Na]i/ [Ca]i in heart failure. However, the role of CaMKII/[Na ]i/[Ca 2+] i feedback in MIRI is still unclear. In the present study, we took the published MIRI action potential model [7,8], 50% blocking the voltage-dependent sodium current(INa) and CaMKII, to observe the effect of INa(-) and CaMKII(-) on MIRI. To ensure the influence of INa and CaMKII on MIRI, we used Roberts-Christini MIRI AP model [7,8], which combined the dynamic changes of intracellular pH (pHi), extracellular pH(pHe), 13 ion currents and 6 pump exchangers. All simulations were run using a pacing rate of 1 Hz. Four groups were set as: Control (MIRI only), INa 50% block, CaMKII 50% block and both (INa 50% and CaMKII 50% block), respectively.