Heart Rate and Rhythm Molecular Basis, Pharmacological Modulation and Clinical Implications

This completely updated and expanded 2nd Edition provides all the information needed in order to understand the complex molecular, cellular and genetic mechanisms that underlie normal and abnormal cardiac rhythms. Its goal is to help physiologists and clinicians alike develop better preventive and treatment strategies.

The respective chapters cover a broad range of topics, including the role of specific ion channels and transporters, gap junctions, intracellular Ca2+ handling in pacemaker activity, impulse conduction, and the activity of atrial and ventricular myocardium. Special emphasis is placed on the unique electrophysiology of specialized pacemaking cells and conducting fibers. In turn, several types of inherited and acquired ventricular arrhythmias are presented in detail. Clinicians will especially appreciate the updated information on even common disorders like atrial fibrillation and their impacts on human physiology.

In closing, the book goes “one step further” and considers future prospects, e.g. novel antiarrhythmic agents and new concepts like optogenetics, in the context of heart rate regulation. Accordingly, it offers readers a solid reference guide to everything they need to know about human heart rate and rhythm.

Part I Normal Cardiac Rhythm and Pacemaker Activity

1 Cardiac Ion Channels and Heart Rate and Rhythm

Onkar Nath Tripathi

2 Ionic Basis of the Pacemaker Activity of SA Node Revealed by the Lead Potential Analysis

Yukiko Himeno, Chae Young Cha, and Akinori Noma

3 The “Funny” Pacemaker Current

Andrea Barbuti, Annalisa Bucchi, Raffaella Milanesi, Georgia Bottelli, Alessia Crespi, and Dario DiFrancesco

4 Novel Perspectives on Cardiac Pacemaker Regulation: Role of the Coupled Function of Sarcolemmal and Intracellular Proteins

Victor A. Maltsev, Tatiana M. Vinogradova, and Edward G. Lakatta

5 Pacemaker Activity of the SA Node: Insights from Dynamic-Clamp Experiments

Ronald Wilders, Antoni C.G. van Ginneken, and Arie O. Verkerk

6 Heart Rate Variability: Molecular Mechanisms and Clinical implications

Kishore K. Deepak

7 Mechano-Electric Feedback in the Heart: Effects on Heart Rate and Rhythm

T. Alexander Quinn, Rebecca A. Bayliss, and Peter Kohl

 

Part II Modeling

8 A Historical Perspective on the Development of Models of Rhythm in the Heart

Penelope J. Noble and Denis Noble

9 Simulation of Cardiac Action Potentials

Jonathan D. Moreno and Colleen E. Clancy

 

Part III Cardiac Development and Anatomy

10 Development of Pacemaker Activity in Embryonic and Embryonic Stem Cell-Derived cardiomyocytes

Huamin Liang, Michael Reppel, Ming Tang, and Ju¨rgen Hescheler

11 Molecular Basis of the Electrical Activity of the Atrioventricular Junction and Purkinje Fibres

Halina Dobrzynski, Oliver Monfredi, Ian D. Greener, Andrew Atkinson, Shin Inada, Mary-Anne Taube, Joseph Yanni, Olga Fedorenko, Peter Molenaar, Robert H. Anderson, Igor R. Efimov, and Mark R. Boyett

12 Molecular Basis and Genetic Aspects of the Development of the Cardiac Chambers and Conduction System: Relevance to Heart Rhythm

Martijn L. Bakker, Vincent M. Christoffels, and Antoon F.M. Moorman

13 Role of the T-Tubules in the Response of Cardiac Ventricular Myocytes to Inotropic interventions

C.H. Orchard, F. Brette, A. Chase, and M.R. Fowler

 

Part IV Mechanisms of Acquired Arrhythmia

14 An Overview of Spiral- and Scroll-Wave Dynamics in Mathematical Models for Cardiac Tissue

Rupamanjari Majumder, Alok Ranjan Nayak, and Rahul Pandit

15 Post-infarction Remodeling and Arrhythmogenesis: Molecular, Ionic, and Electrophysiological substrates

Nabil El-Sherif

16 The Role of Intracellular Ca2+ in Arrhythmias in the Postmyocardial Infarction heart

Wen Dun, Henk ter Keurs, and Penelope A. Boyden

17 Molecular and Biochemical Characteristics of the Intracellular Ca2+ Handling Proteins in the Heart

Yasser Abdellatif, Vijayan Elimban, Delfin Rodriguez-Leyva, and Naranjan S. Dhalla

18 Pharmacological Modulation and Clinical Implications of Sarcolemmal Ca2+-Handling Proteins in Heart Function

Yasser Abdellatif, Adriana Adameova, and Naranjan S. Dhalla

19 Calmodulin Kinase II Regulation of Heart Rhythm and Disease

Thomas J. Hund

20 MicroRNA and Pluripotent Stem Cell-Based Heart Therapies: The Electrophysiological Perspective

Ellen Poon, Deborah K. Lieu, and Ronald A. Li

 

Part V Mechanisms of Inherited Arrhythmia

21 Intracellular Calcium Handling and Inherited Arrhythmogenic Diseases

Nicola Monteforte, Carlo Napolitano, Raffaella Bloise, and Silvia G. Priori

22 Molecular Mechanisms of Voltage-Gated Na+ Channel Dysfunction in LQT3 Syndrome

Thomas Zimmer and Klaus Benndorf

23 The Short QT Syndrome

Jules C. Hancox, Mark J. McPate, Aziza El Harchi, Rona S. Duncan, Chris E. Dempsey, Harry J. Witchel, Ismail Adeniran, and Henggui Zhang

24 Adrenergic Regulation and Heritable Arrhythmias: Key Roles of the Slowly Activating Heart IKs Potassium Channel

David Y. Chung, Kevin J. Sampson, and Robert S. Kass

25 Defects in Ankyrin-Based Protein Targeting Pathways in Human Arrhythmia

Hjalti Gudmundsson, Francis Jareczek, and Peter J. Mohler

26 Genetically Modified Mice: Useful Models to Study Cause and Effect of Cardiac Arrhythmias?

Gregor Sachse, Martin Kruse, and Olaf Pongs

27 Genetics of Atrial Fibrillation

Saagar Mahida, Michiel Rienstra, Moritz F. Sinner, Steven A. Lubitz, Patrick T. Ellinor, and Stefan Ka¨a¨b

 

Part VI Role of Specific Channels and Transporters in Arrhythmia

28 The Role of Gap Junctions in Impulse Propagation in the Heart: New Aspects of Arrhythmogenesis and New Antiarrhythmic Agents Targeting Gap Junctions

Stefan Dhein, Joanna Jozwiak, Anja Hagen, Thomas Seidel, Anna Dietze, Aida Salameh, Martin Kostelka, and Friedrich Wilhelm Mohr

29 Possible Mechanisms of the Acute Ischemia-Induced Ventricular Arrhythmias: The Involvement of Gap Junctions

A´gnes Ve´gh and Rita Papp

30 Role of NCX1 and NHE1 in Ventricular Arrhythmia

Andra´s To´th and Andra´s Varro´

31 TRP Channels in Cardiac Arrhythmia: Their Role During Purinergic Activation Induced by Ischemia

Guy Vassort and Julio Alvarez

32 Cardiac Aquaporins: Significance in Health and Disease

Tanya L. Butler and David S. Winlaw

 

Part VII Drugs and Cardiac Arrhythmia

33 Ion Channels as New Drug Targets in Atrial Fibrillation

Ursula Ravens

34 hERG1 Channel Blockers and Cardiac Arrhythmia

Michael C. Sanguinetti and Matthew Perry

35 Preclinical Drug Safety and Cardiac Ion Channel Screening

Zhi Su and Gary Gintant

36 QT Prolongation Is a Poor Predictor of Proarrhythmia Liability: Beyond QT Prolongation!

Luc M. Hondeghem

37 K Channel Openers as New Anti-arrhythmic Agents

Nathalie Strutz-Seebohm and Guiscard Seebohm

Proposed New Chapters

 

38 Pathways in human arrhythmias: Impact of post-translational modifications in human arrhythmia

Peter Mohler (Ohio State University)

39 Unique features of the human SA node structure, function and arrhythmias: mechanistic insights from integrated 3D mapping approaches

Vadim Fedorov (Ohio State University)

40 Epigenetic Mechanisms in Arrhythmias: New Insights and Future Directions

Loren Wold (Ohio State University)

41 Molecular basis of chronobiology of cardiac rate and rhythm

Narsingh Verma (King Georges Medical University, Lucknow)

42 L-type calcium channels and cardiac arrhythmias

Ian Matthes (Universitaet Koeln)

43 Optogenetics in arrhythmia

Franzisca Schneider-Warme (IEKM, Freiburg)

44 Heterocellular interactions and arrhythmia

Eva Rog-Zielinski (IEKM, Freiburg)

45 Neural regulation of heart rate and rhythm- some fundamental aspects

Onkar Tripathi

Dr. Onkar N. Tripathi received his PhD degree in Pharmacology from King George's Medical University, Lucknow, India. From 1973-1975 he was an Alexander-von-Humboldt Research Fellow in Germany working in the electrophysiology laboratories of Wolfgang Trautwein (Homburg, Saar) and Albrecht Fleckenstein (Freiburg im Breisgau). His research interests are autonomic neural regulation of heart, cardiac cellular electrophysiology and ion channels. Until his retirement, he chaired the Cardiac Electrophysiology Division at the Central Drug Research Institute in Lucknow. 

Dr. Ursula Ravens received her MD from Albert-Ludwigs-University, Freiburg. After an internship in Berlin, she specialized in Pharmacology at University of Kiel. In 1985, she obtained a tenured position as Professor of Cardiovascular Pharmacology at the Medical Faculty of Essen University. In 1994 she did a sabbatical at the National Heart & Lung Institute of Imperial College London. She was appointed to the chair of Pharmacology and Toxicology at the Medical Faculty of TU Dresden in 1997 from which she retired in 2014. Since 2016 she holds a position as senior guest professor at Institute of Experimental Cardiovascular Medicine of University Clinics Freiburg. Her research focuses on cardiac cellular electrophysiology with emphasis on antiarrhythmic drug action on ion channels and stretch-activated channels of human cardiac cells in health and disease, especially atrial fibrillation.

Dr. T. Alexander Quinn received his BSc in Physiology & Physics from McGill University and his PhD in Biomedical Engineering from Columbia University in New York. He did his postdoctoral training in the Depts of Physiology, Anatomy & Genetics and Computer Science at the University of Oxford, where he was a Fulford Junior Research Fellow in Medical Sciences at Somerville College, followed by time at the National Heart & Lung Institute of Imperial College London. He was recruited to the Dept of Physiology & Biophysics at Dalhousie University, in 2013, where he is the Director of the Cardiac Autoregulation & Arrhythmias Laboratory, with a cross-appointment in the School of Biomedical Engineering. His research focuses on the regulation of cardiac electrical activity by processes that reside within the heart itself, and the role that these auto-regulatory mechanisms play in deadly arrhythmias that occur in disease and with ageing.