Calcium calmodulin dependent protein kinase II (CaMKII) contribute to arrhythmias after acidosis: Simulation study

In this paper, to analyze the functional influence of acidosis on cardiac electrical activity and subsequently on ventricular arrhythmia, a human ventricular acidotic model with PH and CaM kinase II (CaMKII) regulation was developed. Dynamic changes of ionic currents and action potentials during the acidosis process were simulated, and the changes of action potential of different conditions (with CaMKII and without CaMKII) were compared during acidosis. In addition the acidosis-induced changes of electrocardiogram waveform were computed using the one-dimensional tissue model. The experimental results showed that in the process of acidosis, CaMKII was highly activated, the concentration of both sodium and calcium within the cell elevated. Especially, at the early stage of the post acidosis, delayed after depolarizations (DADs) were generated in the cellular membrane potential, but DADs would disappear when eliminating the effect of CaMKII on all ion currents. At last, the triggered activities induced in cells during post acidosis period caused ectopic depolarization and ectopic repolarization in the cardiac tissue. Meanwhile, the simulated electrocardiogram showed premature ventricular contractions.