title: Electrophysiological Characteristics of the LQT2 Syndrome MutationKCNH2-G572Sand Regulation by Accessory ProteinKCNE2.
abstract: Mutations inhERGcause long QT syndrome type 2 which is characterized by a prolonged QT interval on electrocardiogram and predisposition to life-threatening ventricular tachyarrhythmia, syncope, and sudden death.hERG-G572Sinduces trafficking defects ofhERGchannel protein from Golgi to the plasma membrane and results in a dominant negative suppression ofhERGcurrent density. As an accessory β subunit,KCNE2promoteshERGmigration from Golgi to cellular membrane. In this study, we investigated the rescue effect ofKCNE2in aG572Smutation ofhERG. Transfection was performed into HEK293 cells. Patch clamp technique, western blotting analyses and confocal microscopic examination were used. Results showed thatKCNE2had a significantly enhanced effect onG572Smutation current. The increase of current was largest atKCNH2:KCNE2of 1:3. Confocal images showed co-expressingG572SandKCNE2could cause a substantial up-regulated membrane protein (155 kDa) expression. Expression of membrane protein accumulated markedly with increasing ratio ofKCNH2:KCNE2.G572Sdefective mutant could be restored by bothKCNE2and lower temperature (27°C), which suggested that the lower temperature could be the favorable circumstances for the rescue function ofKCNE2. In this study, we successfully set up "the action potential" on the HEK 293 cells by genetically engineered to express Kir2.1, Nav1.5, and Kv11.1, wherein on reaching over an excitation threshold by current injection. The results suggested thatKCNE2could shorten action potential duration which was prolonged byG572S. These findings described electrophysiological characteristics of the LQT2 syndrome mutationKCNH2-G572Sand regulation by accessory proteinKCNE2, and provided a clue about LQT2 and relative rescue mechanism.
authors.affiliation: Department of Cardiology, General Hospital of People's Liberation ArmyBeijing, China; The Third Department of Internal Medicine, Beijing Municipal Corps Hospital of Chinese People's Armed Police ForceBeijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Cardiology, General Hospital of People's Liberation Army Beijing, China.
authors.forename: Jinwen
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Cardiology, General Hospital of People's Liberation Army Beijing, China.
authors.forename: Caiyi
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Cardiology, General Hospital of People's Liberation Army Beijing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Cardiology, General Hospital of People's Liberation Army Beijing, China.
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Cardiology, General Hospital of People's Liberation Army Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Cardiology, General Hospital of People's Liberation Army Beijing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, General Hospital of People's Liberation Army Beijing, China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Cardiology, General Hospital of People's Liberation Army Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, General Hospital of People's Liberation Army Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, General Hospital of People's Liberation Army Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
keywords: KCNE2; KCNH2; action potential; long QT syndrome type 2; low temperature; trafficking