title: [Electrophysiological characterization of long QT syndrome associated mutations V630A and N633S].
abstract: 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.
authors.affiliation: Department of Internal Medicine, Cardiovascular Hospital of Qinghai Province, Xining 810012, China.
authors.forename: Hai-ru
authors.initials: HR
authors.lastname: She
authors.forename: Si-yong
authors.initials: SY
authors.lastname: Teng
authors.forename: Jie-lin
authors.initials: JL
authors.lastname: Pu
authors.forename: Zheng-lu
authors.initials: ZL
authors.lastname: Shang
authors.forename: Ru-tai
authors.initials: RT
authors.lastname: Hui
mesh_terms: 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
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D018075:RNA, Complementary