title: Utility of hERG assays as surrogate markers of delayed cardiac repolarization and QT safety.
abstract: HERG (human-ether-a-go-go-related gene) encodes for a cardiac potassium channel that plays a critical role in defining ventricular repolarization. Noncardiovascular drugs associated with a rare but potentially lethal ventricular arrhythmia (Torsades de Pointes) have been linked to delayed cardiac repolarization and block of hERG current. This brief overview will discuss the role of hERG current in cardiac electrophysiology, its involvement in drug-induced delayed repolarization, and approaches used to define drug effects on hERG current. In addition, examples of hERG blocking drugs acting differently (i.e., overt and covert hERG blockade due to multichannel block) together with the utility and limitations of hERG assays as tools to predict the risk of delayed repolarization and proarrhythmia are discussed.
authors.affiliation: Deptartment of Integrative Pharmacology, Abbott Laboratories, Abbott Park, Illinois 60064-6119, USA. Gary.Gintant@abbott.com
authors.forename: Gary A
authors.initials: GA
authors.lastname: Gintant
authors.forename: Zhi
authors.initials: Z
authors.lastname: Su
authors.forename: Ruth L
authors.initials: RL
authors.lastname: Martin
authors.forename: Bryan F
authors.initials: BF
authors.lastname: Cox
mesh_terms: D000818:Animals; D000830:Animals, Laboratory; D015415:Biomarkers / Q000378:metabolism; D064420:Drug-Related Side Effects and Adverse Reactions; D051638:Ether-A-Go-Go Potassium Channels / Q000502:physiology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006329:Heart Conduction System / Q000378:metabolism / Q000503:physiopathology*; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D004364:Pharmaceutical Preparations / Q000145:classification; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D051638:Ether-A-Go-Go Potassium Channels; D004364:Pharmaceutical Preparations