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4.0
76 reviewsIt 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.Content:
Chapter 1 Chair's Introduction (pages 1–3): Michael C. Sanguinetti
Chapter 2 Gating and Assembly of Heteromeric hERG1a/1b Channels Underlying IKr in the Heart (pages 4–18): Gail A. Robertson, Eugenia M.C. Jones and Jinling Wang
Chapter 3 Structure–Function Studies of the Outer Mouth and Voltage Sensor Domain of hERG (pages 19–43): Gea?Ny Tseng and H. Robert Guy
Chapter 4 General Discussion I (pages 44–45):
Chapter 5 Voltage Sensor Movement in the hERG K+ Channel (pages 46–56): David R. Piper, Michael C. Sanguinetti and Martin Tristani?Firouzi
Chapter 6 hERG Channel Trafficking (pages 57–74): Eckhard Ficker, Adrienne Dennis, Yuri Kuryshev, Barbara A. Wible and Arthur M. Brown
Chapter 7 Dynamic Control of hERG/IKr by PKA?Mediated Interactions with 14?3?3 (pages 75–94): Anna Kagan and Thomas V. McDonald
Chapter 8 General Discussion II (pages 95–99):
Chapter 9 Does hERG Coassemble with a ? Subunit? Evidence for Roles of MinK and MiRP1 (pages 100–117): Arun Anantharam and Geoffrey W. Abbott
Chapter 10 hERG Block, QT Liability and Sudden Cardiac Death (pages 118–135): Arthur M. Brown
Chapter 11 Structural Determinants for High?Affinity Block of hERG Potassium Channels (pages 136–154): John Mitcheson, Matthew Perry, Phillip Stansfeld, Michael C. Sanguinetti, Harry Witchel and Jules Hancox
Chapter 12 General Discussion III (pages 155–158):
Chapter 13 Physicochemical Basis for Binding and Voltage?Dependent Block of hERG Channels by Structurally Diverse Drugs (pages 159–170): Michael C. Sanguinetti, Jun Chen, David Fernandez, Kaichiro Kamiya, John Mitcheson and Jose A. Sanchez?Chapula
Chapter 14 In Silico Modelling?Pharmacophores and hERG Channel Models (pages 171–185): Maurizio Recanatini, Andrea Cavalli and Matteo Masetti
Chapter 15 The Long QT Syndrome: A Clinical Counterpart of hERG Mutations (pages 186–203): Peter J. Schwartz
Chapter 16 Cellular Mechanisms of Torsade de Pointes (pages 204–224): Steven Poelzing and David S. Rosenbaum
Chapter 17 Expression and Role of hERG Channels in Cancer Cells (pages 225–234): Annarosa Arcangeli
Chapter 18 TRIad: Foundation for Proarrhythmia (Triangulation, Reverse Use Dependence and Instability) (pages 235–250): Luc M. Hondeghem
Chapter 19 Drug?Induced QT Interval Prolongation—Regulatory Guidance and Perspectives on hERG Channel Studies (pages 251–285): Dr. Rashmi R Shah
Chapter 20 Closing Remarks (pages 286–287): Michael C. Sanguinetti