Background Gain of function hERG channel caused by a mutation (N588K) has been shown to be associated with Short QT syndrome SQTS type 1(SQTS1). This study was aimed to investigate alterations of hERG channel gating kinetics induced by the mutation (N588K) in hERG-gene.
Methods The human-induced pluripotent stem cell-derived cardiomyocytes (hiPSCs) from three healthy donors and a patient with short QT syndrome type 1 carrying a mutation (N588K) in KCNH2 (hERG) and patch clamp techniques were used for the study.
Results The hERG channel current (IKr) was enhanced in hiPSC-CMs from the SQTS-patient, consistent with a gain-of-function in N588K-hERG channels. The activation curve in SQTS1-hiPSC-CMs was slightly shifted to more positive potentials. The time to peak in SQTS1-hiPSC-CMs was longer than that in healthy donor-hiPSC-CMs. The voltage-dependent inactivation curve in SQTS1-hiPSC-CMs shifted largely to more positive potentials and the time constant of inactivation was largely increased. The recovery from inactivation of IKr in SQTS1-hiPSC-CMs was accelerated and the deactivation was accelerated, too. Furthermore, the window current in SQTS1-hiPSC-CMs was significantly larger than that in donor-hiPSC-CMs. 
Conclusions The gene mutation (N588K) changed the gating kinetics of hERG channels including activation, inactivation recovery and deactivation, which may contribute to the occurrence of arrhythmias in SQTS-patients.