The hERG Cardiac Potassium Channel: Structure, Function and Long QT Syndrome, Novartis Foundation Symposium (Novartis Foundation Symposia)

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

The human ether-á-go-go-related gene (hERG) channel is one of several ion channels involved in the normal action potential repolarization in cardiac myocytes. This book aims to provide a better understanding of the role of the hERG channel in drug-induced cardiac arrhythmias. Contributions from basic, pharmaceutical, and clinical sciences and regulatory authority perspectives examine the structure and function of hERG, the molecular basis for compound binding, and preferred preclinical test systems. Coverage encompasses hERG channel gating, trafficking, and pharmacology, and mechanisms of drug-induced LQTS. Annotation ©2005 Book News, Inc., Portland, OR

Doody Review Services

Reviewer:Ruben D Bunag, MD, MA Pharmacology(University of Kansas Medical Center)
Description:The book describes papers presented at a symposium on the hERG cardiac potassium channel structure, function, and long QT syndrome, held at the Novartis Foundation in London, May 4-6, 2004.
Purpose:From the chair's introduction, the three topics chosen for discussion are: the structural basis of function of hERG channels; the physiological roles of hERG channels; and related mechanisms of drug-induced long QT syndrome (LQTS). These are worthy objectives for understanding what cardiac hERG channels do and how they participate in producing drug-induced LQTS. Of the multiple potassium currents that mediate repolarization of the cardiac action potential, the Ikr current is conducted by hERG channels which are important not only for action potential repolarization, but also for SA and AV node pacemaking.
Audience:This book is mainly for clinical cardiologists and drug company researchers concerned with cardiac drug toxicity involving LQTS, Torsade de Pointes, and sudden cardiac death. The authors are among leading authorities on the subject matter.
Features:Text descriptions are generally divided into four parts. The first part addresses questions concerning hERG channel gating, deactivation rates, residue interactions and how they control voltage sensor movement. The second part covers hERG channel trafficking, modulation of hERG, and the role of accessory subunits. The third part is mainly on hERG pharmacology and the usefulness of pharmacophore models for in silico predictions of hERG channel blocker potency. The final part then addresses mechanisms of drug-induced LQTS and Torsade de Pointes that may result in sudden cardiac death.
Assessment:The book is well written and organized and will serve as a useful reference for current literature and developments on the cardiac hERG potassium channel. No other books are currently available on the subject.

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/IKr channels, drug-induced long QT syndrome and preclinical evaluation and regulatory recommendations for assessing QT prolongation risks. "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."--Jacket The three topics chosen for discussion by the organizers of this meeting are (1) the structural basis of function of hERG channels, (2) the physiological roles of hERG channels and (3) mechanisms of drug-induced long QT syndrome (LQTS).