hERG Cardiac Potassium Channel (eBook)

Structure, Function and Long QT Syndrome
eBook Download: PDF
2005 | 1. Auflage
312 Seiten
Wiley (Verlag)
978-0-470-02141-5 (ISBN)

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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.



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.
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 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.

Chair's introduction (Michael Sanguinetti).

Gating and assembly of heteromeric hERG1a/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 hERG (Gea-Ny Tseng and H. Robert Guy).

General Discussion I.

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

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

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

General Discussion II.

Does hERG coassemble with a ß subunit? Evidence for
roles 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 hERG
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
hERG 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 hERG channel
models (Maurizio Recanatini, Andrea Cavalli and
MatteoMasetti).

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 hERG channel studies (Rashmi R. Shah).

Closing remarks (Michael Sanguinetti).

Index of contributors.

Subject index.

"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)

Erscheint lt. Verlag 14.6.2005
Reihe/Serie Novartis Foundation Symposium
Sprache englisch
Themenwelt Studium 1. Studienabschnitt (Vorklinik) Physiologie
Naturwissenschaften Biologie Mikrobiologie / Immunologie
Technik
Schlagworte Biowissenschaften • Cell & Molecular Biology • Life Sciences • Molekularbiologie • Zell- u. Molekularbiologie
ISBN-10 0-470-02141-1 / 0470021411
ISBN-13 978-0-470-02141-5 / 9780470021415
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