Unit

UNIT 10.15 Whole-Cell Configuration of the Patch-Clamp Technique in the hERG Channel Assay to Predict the Ability of a Compound to Prolong QT Interval

  1. Sonia Goineau,
  2. Christophe Legrand,
  3. Guillaume Froget

Published Online: 1 JUN 2012

DOI: 10.1002/0471141755.ph1015s57

Current Protocols in Pharmacology

Current Protocols in Pharmacology

How to Cite

Goineau, S., Legrand, C. and Froget, G. 2012. Whole-Cell Configuration of the Patch-Clamp Technique in the hERG Channel Assay to Predict the Ability of a Compound to Prolong QT Interval. Current Protocols in Pharmacology. 57:10.15:10.15.1–10.15.14.

Author Information

  1. Porsolt Research Center, Le Genest-Saint-Isle, France

Publication History

  1. Published Online: 1 JUN 2012
  2. Published Print: JUN 2012

Abstract

In vitro electrophysiological safety studies have become an integral part of the drug development process since, in many instances, compound-induced QT prolongation has been associated with a direct block of human ether-a-go-go-related gene (hERG) potassium channels or its native current, the rapidly activating delayed rectifier potassium current (IKr). Therefore, the in vitro hERG channel patch-clamp assay is commonly used as an early screen to predict the ability of a compound to prolong QT interval. The protocol described in this unit is designed to assess the effects of new chemical entities after acute or long-term exposure on the amplitude of IKr in human embryonic kidney 293 (HEK293) cells stably transfected with the hERG channel (whole-cell configuration of the patch-clamp technique). Examples of results obtained with terfenadine, arsenic, pentamidine, erythromycin, and sotalol are provided for illustrative purposes. Curr. Protoc. Pharmacol. 57:10.15.1-10.15.14. © 2012 by John Wiley & Sons, Inc.

Keywords:

  • hERG;
  • patch-clamp;
  • whole-cell configuration;
  • QT prolongation;
  • trafficking