Investigation of the functional effects of KCNJ2-linked short QT syndrome on electrical conduction at purkinje-ventricle junction at low- and high- frequencies

Recent studies suggested that genetic KCNJ2-linked short QT syndrome (SQT3) arises due to IK1 mutations leading to accelerated ventricular repolarization, arrhythmias. However, ionic mechanisms underlying cardiac arrhythmias of SQT3 are incompletely understood. Our goal was to investigate the functional impacts of SQT3 on the electrical wave conduction at the Purkinje-ventricle junction (PVJ). In the computational simulations, compared with 1.25 Hz of electrical stimulation, the measured APD90 did not change noticeably at 0.5 Hz, but was reduced at 2.66 Hz. At 3.33 Hz, 1:1 response of electrical excitation wave propagation to stimuli failed in WT condition, but sustained in mutation conditions. This suggested that increased IK1 accelerates ventricular repolarization, and reduces APD spatial dispersion along the tissue, which facilitates the conduction of rapid electrical excitation waves in contrast to conduction failure in the WT condition. Such a loss of protective effect at high frequency of electrical stimulation, together with abbreviated APD and ERP, may account for the initiation of ventricular tachycardia and fibrillation.