[Electrophysiological characterization of long QT syndrome associated mutations V630A and N633S].
OBJECTIVE
To identify the electrophysiological properties of long-QT syndrome (LQTS) associated missense mutations in the outer mouth of the HERG potassium channel in vitro.


METHODS
Mutations V630A and N633S were constructed by Megaprimer PCR method and cRNA were produced by T7 RNA polymerase. The electrophysiological properties of the mutation were investigated in the Xenopus oocyte heterologous expression system.


RESULTS
Coexpression of mutant and wild-type HERG subunits caused a dominant-negative effect, and the currents were significantly decreased. Compared with wild-type HERG channels, V630A and N633S mutations were related to decreased time constants for inactivation for V630A/WT and N633S/WT at all potentials, reduced slope conductance and the voltage dependence of steady-state inactivation was shifted to negative potentials for V630A/WT and N633S/WT.


CONCLUSIONS
Present study shows that LQTS associated missense mutations located in the outer mouth of HERG cause a dominant-negative effect and alterations in steady-state voltage dependence of channel gating of heteromultimeric channels suggesting a reduction in expressional current might be one of the pathophysiologic mechanisms of LQTS.
She
Hai-ru
HR
Department of Internal Medicine, Cardiovascular Hospital of Qinghai Province, Xining 810012, China.
Teng
Si-yong
SY
Pu
Jie-lin
JL
Shang
Zheng-lu
ZL
Hui
Ru-tai
RT
D000818:Animals; D004252:DNA Mutational Analysis; D000072237:ERG1 Potassium Channel; D004562:Electrocardiography; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics*; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics*; D020125:Mutation, Missense; D009865:Oocytes; D018408:Patch-Clamp Techniques; D018075:RNA, Complementary; D014981:Xenopus
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D018075:RNA, Complementary