Whole-cell configuration of the patch-clamp technique in the hERG channel assay to predict the ability of a compound to prolong QT interval.
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 (I(Kr)). 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 I(Kr) 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.
Porsolt Research Center, Le Genest-Saint-Isle, France.
Sonia
S
Goineau
Christophe
C
Legrand
Guillaume
G
Froget
D003627:Data Interpretation, Statistical; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control*; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000187:drug effects*; D057809:HEK293 Cells; D006801:Humans; D007202:Indicators and Reagents; D008133:Long QT Syndrome / Q000139:chemically induced*; D018408:Patch-Clamp Techniques / Q000379:methods*
D051638:Ether-A-Go-Go Potassium Channels; D007202:Indicators and Reagents