Simulation of KCNJ2-linked Short QT syndrome in human ventricular tissue

In the present study we developed a computer models of human ventricular cell and tissue to simulate SQT3 syndrome that is associated with gain-in-function of I
_K1
channel arising from KCNJ2 gene mutation. We explored the functional effects of Kir2.1 D172N mutation-induced changes in I
_K1
on the electrical action potentials (APs) of cardiac cells and electrical wave conduction in ventricular tissues. Two scenarios were considered: one considered wild type (WT), heterozygous (WT-D172N) and homozygous (D172N), the other considered EPI, MIDDLE, ENDO cell types in heterogeneous ventricular wall. In cellular simulations, we computed action potential duration (APD), current traces of I
_k1
during APs. In 2D tissue simulations, the functional effects of the SQT3 on the characteristics of ECG were computed. It was shown that under the SQT3 condition, the action potential duration was abbreviated, magnitude of I
_k1
current during APs was increased and QT interval in pseudo- ECG was abbreviated dramatically. Such changes under the D172N condition were more remarkable than those under the WT-D172N condition. In conclusion, increased I
_k1
associated with SQT3 condition accelerates ventricular repolarization, which may increase arrhythmogeneity of ventricular fibrillation leading to sudden cardiac death.