Correlation between human ether-a-go-go-related gene channel inhibition and action potential prolongation.

ABSTRACT:

Background and purpose

Human ether-a-go-go-related gene (hERG; K_v 11.1) channel inhibition is a widely accepted predictor of cardiac arrhythmia. hERG channel inhibition alone is often insufficient to predict pro-arrhythmic drug effects. This study used a library of dofetilide derivatives to investigate the relationship between standard measures of hERG current block in an expression system and changes in action potential duration (APD) in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The interference from accompanying block of Ca_v 1.2 and Na_v 1.5 channels was investigated along with an in silico AP model.

Experimental approach

Drug-induced changes in APD were assessed in hiPSC-CMs using voltage-sensitive dyes. The IC

SUBMITTER: Saxena P 

PROVIDER: S-EPMC5573420 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature