Abstract
Blockade of the cardiac ion channel coded by human ether-à-gogo-related gene (hERG) can lead to cardiac arrhythmia, which has become a major concern in drug discovery and development. Automated electrophysiological patch clamp allows assessment of hERG channel effects early in drug development to aid medicinal chemistry programs and has become routine in pharmaceutical companies. However, a number of potential sources of errors in setting up hERG channel assays by automated patch clamp can lead to misinterpretation of data or false effects being reported. This article describes protocols for automated electrophysiology screening of compound effects on the hERG channel current. Protocol details and the translation of criteria known from manual patch clamp experiments to automated patch clamp experiments to achieve good quality data are emphasized. Typical pitfalls and artifacts that may lead to misinterpretation of data are discussed. While this article focuses on hERG channel recordings using the QPatch (Sophion A/S, Copenhagen, Denmark) technology, many of the assay and protocol details given in this article can be transferred for setting up different ion channel assays by automated patch clamp and are similar on other planar patch clamp platforms.
Highlights
A number of drug discovery and development programs have been hampered by issues with drug induced cardiac arrhythmia
Blockade of the cardiac ion channel coded by human ether-à-gogo-related gene can lead to cardiac arrhythmia, which has become a major concern in drug discovery and development
While this article focuses on human ether-à-gogo-related gene (hERG) channel recordings using the QPatch (Sophion A/S, Copenhagen, Denmark) technology, many of the assay and protocol details given in this article can be transferred for setting up different ion channel assays by automated patch clamp and are similar on other planar patch clamp platforms
Summary
A number of drug discovery and development programs have been hampered by issues with drug induced cardiac arrhythmia. HERG CHANNEL BLOCKADE CAN CAUSE CARDIAC ARRHYTHMIA Nearly 20 years ago it was found that mutations in the hERG could cause long QT syndrome This inherited disorder can be observed in the electrocardiogram as prolonged QT interval and is correlated to torsades de pointes ventricular tachyarrhythmia (Curran et al, 1995; Sanguinetti et al, 1995; Sanguinetti and Tristani-Firouzi, 2006). While compounds from very different chemical classes may interact with the hERG channel due to its relatively large hydrophobic pore, the property of hERG channel liability has been observed especially often for histamine receptor antagonists. The reason for this is that the pharmacophores of the hERG www.frontiersin.org
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
