Electrophysiological Study of V535M hERG Mutation of LQT2
10.1007/sl1596-011-0670-2
- Author:
SHAO CHUNYAN
1
;
LU YAN
;
LIU MOHAN
;
CHEN QI
;
LAN YUNFENG
;
LIU YAN
;
LIN MIN
;
LI YANG
Author Information
1. Institute of Geriatric Cardiology of Chinese PLA General Hospital, Beijing 100853, China
- Keywords:
ion channel;
long QT2 syndrome;
human ether-a-go-go-related gene current;
cardiac arrhythmia
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2011;31(6):741-748
- CountryChina
- Language:Chinese
-
Abstract:
This study examined the current changes of human ether-a-go-go-related gene (hERG) mutation derived from a LQT2 Chinese family with a highly penetrating phenotype.Mutation was identified and site-directed mutagenesis was performed to induce the mutation in wild-type (WT) hERG.WT hERG and mutated V535M were cloned and transiently expressed in HEK293 cells.At the 48th and 72nd h after transfection,membrane currents were recorded using whole cell patch-clamp procedures.An A＞G transition at 1605 resulting in replacement of V535M was identified.Compared to WT,V535M mutation significantly decreased tail currents of hERG.At test potential of-40 mV after depolarizing at +50 mV,tail current densities were 83.35±7.06 pA/pF in WT and 50.38±7.74 pA/pF in V535M respectively (n=20,P＜0.01).Gating kinetics of hERG revealed that V1/2 of steady-state inactivation shifted to negative potential in the mutant (V1/2,V535M:-61.81±1.7 mV vs.V1/2,WT:-43.1±0.71mV).The time constant of recovery from inactivation was markedly prolonged in the mutant compared to WT among test potentials.V535M hERG mutation demonstrated markedly decreased tail current densities,which suggests that V535M is a new loss-of-function mutation of bERG channel responsible for LQT2.
