Derek J. Chadwick & Jamie A. Goode 
The hERG Cardiac Potassium Channel [PDF ebook] 
Structure, Function and Long QT Syndrome

This book draws together contributions from basic, pharmaceutical
and clinical sciences aimed at a better understanding of the
structure and function of h ERG and the molecular basis for compound
binding.

It features regulatory authority perspectives on preferred
preclinical test systems and includes topics on h ERG channel
gating, regulation of functional expression, pharmacological
properties of h ERG/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 h ERG channel in
drug-induced cardiac arrhythmias should ultimately lead to the
development of important, new and safer medicines.

Inhaltsverzeichnis

Chair’s introduction (Michael Sanguinetti).

Gating and assembly of heteromeric h ERG1a/1b channels
underlying IKr in the heart (Gail A.
Robertson, Eugenia M. C. Jones and Jinling Wang).

Structure-function studies of outer mouth and voltage sensor
domain of h ERG (Gea-Ny Tseng and H. Robert Guy).

General Discussion I.

Voltage sensor movement in the h ERG K¯+ channel (David
R. Piper, Michael C. Sanguinetti and Martin Tristani-Firouzi).

h ERG channel trafficking (Eckhard Ficker, Adrienne Dennis, Yuri
Kuryshev, Barbara A.Wible and Arthur M. Brown).

Dynamic control of h ERG/IKrr by
PKA-mediated interactions with 14-3-3 (Anna Kagan and Thomas V.
Mc Donald).

General Discussion II.

Does h ERG coassemble with a ß subunit? Evidence for
roles of Min K and Mi RP1 (Arun Anantharam and Geoffrey W.
Abbott).

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

Structural determinants for high affinity block of h ERG
potassium channels ( John Mitcheson, Matthew Perry, Phillip
Stansfeld, Mike Sanguinetti, Harry Witchel and Jules Hancox).

General Discussion III.

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

In silico – modelling pharmacophores and h ERG channel
models (Maurizio Recanatini, Andrea Cavalli and
Matteo Masetti).

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

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

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

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

Drug-induced QT interval prolongation: regulatory guidance and
perspectives on h ERG channel studies (Rashmi R. Shah).

Closing remarks (Michael Sanguinetti).

Index of contributors.

Subject index.

Über den Autor

The Novartis Foundation is an international scientific and educational charity that promotes the study and general knowledge of science and in particular encourages international co-operation in scientific research.