The hERG Cardiac Potassium Channel / Edition 1

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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.

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Editorial Reviews

Doody's Review Service
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.
From the Publisher
“This is a fantastic collection of hERG channel-related papers, with discussion from experts in the field raising questions yet to be answered.” (The Biochemist, 1 December 2012)

"…a useful reference for current literature and developments on the cardiac hERG potassium channel. No other books are currently available on the subject." (Doody's Health Services)

2 Stars from Doody
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Product Details

  • ISBN-13: 9780470021408
  • Publisher: Wiley
  • Publication date: 4/8/2005
  • Series: Novartis Foundation Symposia Series
  • Edition number: 1
  • Pages: 308
  • Product dimensions: 6.24 (w) x 9.45 (h) x 0.78 (d)

Table of Contents

Chair’s introduction (Michael Sanguinetti).

Gating and assembly of heteromeric hERG1a/1b channelsunderlying  IKr in the heart (Gail A.Robertson, Eugenia M. C. Jones and Jinling Wang).

Structure-function studies of outer mouth and voltage sensordomain of hERG (Gea-Ny Tseng and H. Robert Guy).

General Discussion I.

Voltage sensor movement in the hERG K+ channel (DavidR. Piper,Michael C. Sanguinetti and Martin Tristani-Firouzi).

hERG channel trafficking (Eckhard Ficker, Adrienne Dennis,YuriKuryshev, Barbara A.Wible and Arthur M. Brown).

Dynamic control of hERG/IKrr byPKA-mediated interactions with 14-3-3 (Anna Kagan and Thomas V.McDonald).

General Discussion II.

Does hERG coassemble with a ß subunit? Evidence forroles of MinK and MiRP1 (Arun Anantharam and Geoffrey W.Abbott).

hERG block, QT liability and sudden cardiac death (Arthur M.Brown).

Structural determinants for high affinity block of hERGpotassium channels ( John Mitcheson, Matthew Perry, PhillipStansfeld,Mike Sanguinetti,Harry Witchel and Jules Hancox).

General Discussion III.

Physicochemical basis for binding and voltage-dependent block ofhERG channels by structurally diverse drugs (Michael C.Sanguinetti, Jun Chen, David Fernandez, Kaichiro Kamiya,JohnMitcheson and José A. Sanchez-Chapula). 

In silico - modelling pharmacophores and hERG channelmodels (Maurizio Recanatini, Andrea Cavalli andMatteoMasetti).

The long QT syndrome: a clinical counterpart of HERG mutations(Peter J. Schwartz).

Cellular mechanisms of Torsade de Pointes (Steven Poelzingand David S. Rosenbaum).

Expression and role of HERG channels in cancercells (Annarosa Arcangeli).

TRIad: foundation for proarrhythmia (triangulation, reverse usedependence and instability) (Luc M. Hondeghem).

Drug-induced QT interval prolongation: regulatory guidance andperspectives on hERG channel studies (Rashmi R. Shah).

Closing remarks (Michael Sanguinetti).

Index of contributors.

Subject index.

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