hERG encodes the pore-forming subunit of the rapid component of the delayed rectifier potassium current in cardiac mycoytes, I_Kr. Physiologically, it is one of several ion channels involved in the normal action potential repolarization in cardiac myocytes. Pharmacologically, it is the target for class III antiarrhythmic agents, e.g. quinidine, amiodarone and dofetilide. Toxicologically, it is considered to demonstrate promiscuous binding to a wide range of structurally diverse compounds leading to prolongation of the QT interval. This drug-induced QT interval prolongation, leading to risk of ventricular tachyarrhythmia, Torsade de Pointes and mortality, has precipitated the withdrawal of medicines from the market, particularly amongst certain therapeutic classes including antihistamines, gastrointestinal prokinetics, antipsychotics and antibiotics.

This book draws together contributions from basic, pharmaceutical and clinical sciences and regulatory authority perspectives aimed at a better understanding of the structure and function of hERG, the molecular basis for compound binding and preferred preclinical test systems. Topics include hERG channel gating, regulation of functional expression, pharmacological properties of hERG/I_Kr channels, drug-induced long QT syndrome and preclinical evaluation and regulatory recommendations for assessing QT prolongation risks. It is hoped that a better understanding of the role of the hERG channel in drug-induced cardiac arrhythmias will lead to the development of new and safer medicines.