Volume 4, Issue 2 e959
PROTOCOL

Whole-Cell Configuration of the Patch-Clamp Technique in the hERG Channel Assay

Sonia Goineau

Corresponding Author

Sonia Goineau

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

Corresponding author: [email protected]

Contribution: Writing - original draft

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Lucie Gallet

Lucie Gallet

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

Contribution: Writing - review & editing

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Guillaume Froget

Guillaume Froget

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

Contribution: Visualization

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First published: 09 February 2024

Published in the Pharmacology section

Abstract

In vitro electrophysiological safety studies have become an integral part of the drug development process because, 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 their native current, the rapidly activating delayed rectifier potassium current (IKr). Therefore, according to the ICH S7B guideline, the in vitro hERG channel patch-clamp assay is commonly used as an early screen to predict the ability of a compound to prolong the QT interval prior to first-in-human testing. The protocols described in this article are designed to assess the effects of acute or long-term exposure to new chemical entities on the amplitude of IKr in HEK293 cells stably transfected with the hERG channel (whole-cell configuration of the patch-clamp technique). Examples of results obtained with moxifloxacin, terfenadine, arsenic, pentamidine, erythromycin, and sotalol are provided for illustrative purposes. © 2024 Wiley Periodicals LLC.

Basic Protocol: Measurement of the acute effects of test items in the hERG channel test

Alternate Protocol: Measurement of the long-term effects of test items in the hERG channel test

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.