[Analysis and analyzing mechanisms of HERG channel kinetics]

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2008 Oct;25(5):1068-73.
[Article in Chinese]

Abstract

We have investigated the methods and mechanisms for analysis of the channel kinetics parameters of voltage-gated potassium channels, HERG (Human ether-à-go-go related gene) channels, in the process of electrophysiological recording. The current of HERG K+ channels expressed in Xenopus oocytes was studied using a two-electrode voltage clamp technique, and the channel kinetics parameters were analyzed through compiling different pulse protocol and recording the current. Results showed: (1) The HERG K+ channels, under conditions of being activated with depolarized pulse, expressed an inward-rectified property attributing to rapid inactivation. The activation curve could be obtained through fitting the depolarized potential and the following peak amplitude of tail current, while the parameters of time-dependent activation was obtained through fitting different depolarized duration and the corresponding peak amplitude of tail current. (2) The I-V relationship still exhibit marked inward rectification. Tail current decay traces were fitted with a bi-exponential function to determine the time constants of the fast and slow components of current decay. (3) The inactivation of HERG channels is voltage-dependent. The inactivation process was isolated with two different three-pulse protocols, with which the inactivation curve and nearly linear I-V relationship were obtained, respectively. Thus, altough the kinetics properties of HERG channels were complicated, the channels kinetics could be indirectly analyzed through differently designed pulse protocols, which provided the basis for investigation on Alanine-scanning mutagenesis and agent action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels / analysis*
  • Ether-A-Go-Go Potassium Channels / genetics*
  • Humans
  • Kinetics
  • Oocytes / metabolism
  • Patch-Clamp Techniques
  • Xenopus laevis / metabolism

Substances

  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels
  • KCNH2 protein, human