Referenced in: none

Automatically associated channels: Kv11.1

Title: Automated tight seal electrophysiology for assessing the potential hERG liability of pharmaceutical compounds.

Authors: Huimin Tao, David Santa Ana, António Guia, Mingxian Huang, Joseph Ligutti, George Walker, Khachonesine Sithiphong, Florence Chan, Tao Guoliang, Zoya Zozulya, Steve Saya, Rick Phimmachack, Charles Sie, Julian Yuan, Lei Wu, Jia Xu, Andrea Ghetti

Journal, date & volume: , 2004 Oct , 2, 497-506

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15671647

Abstract
Unintended inhibition of the cardiac potassium channel human ether-a-go-go-related gene (hERG) is considered the main culprit in drug-induced arrhythmias known as torsades de pointes. Electrophysiology is the most reliable in vitro screening method for identifying potential cardiac hERG liabilities, but only the recent advent of planar electrode-based voltage clamp electrophysiology promises sufficient throughput to support the drug testing needs of most drug discovery programs. We have assessed the reliability of this new format of the voltage clamp technology in measuring the activity of small molecules on the hERG channel. Based on the results herein of a screening against a panel of well-characterized hERG-active and -inactive molecules, we demonstrate that planar electrode electrophysiology, utilizing the Sealchip and PatchXpress technology platform (AVIVA Biosciences Corp., San Diego, CA), is comparable to traditional electrophysiology based on glass micropipettes in its reliability and data content. The new technology will allow significantly higher throughput and more thorough testing of pharmaceutical compounds.