An Essential Introduction To Cardiac Electrophysiology

by Kenneth T Macleod

Overview

This book provides undergraduate and postgraduate students with an accessible and comprehensive overview of the fascinating area of cardiac electrophysiology. Using plain language and well-designed illustrations, it attempts to overcome the preconceptions of the subject as difficult to approach, given the complexity of intricate electrical cellular processes within the human heart. Based on lectures presented to intercalating BSc medical students, this book has been designed with the undergraduate in mind, but offers enough scope to be worthwhile at the postgraduate level.Readers of this book will feel more confident and at ease with electrical concepts and the important physiological mechanisms that govern the initiation and regulation of the heartbeat. This volume intends to bridge that difficult region between basic undergraduate lecture notes and original papers in an approachable way. It will be useful to students studying medicine, physiology, pharmacology, pharmacy and biology, particularly where their curricula includes not only cardiac physiology, but also neurobiology and muscle physiology.

Product Details

ISBN-13:	9781908977359
Publisher:	Imperial College Press
Publication date:	01/16/2014
Pages:	288
Product dimensions:	5.90(w) x 8.90(h) x 0.50(d)

Table of Contents

Preface xiii

Chapter 1 Introduction 1

1.1 Early references to the heart and its function 1

1.2 Early references to electrical properties 3

1.3 The electrocardiograph 4

1.4 Cellular electrophysiology 7

1.5 Heart anatomy and location 7

1.6 How this book is organized 13

1.7 Bibliography 15

Chapter 2 The Resting Membrane Potential 17

2.1 Chapter objectives 17

2.2 How is the resting membrane potential generated? 17

2.2.1 What is the Nernst equation? 20

2.2.2 How does changing the potential difference affect ion flow? 22

2.3 K⁺ ion and the membrane potential 22

2.3.1 What are the equilibrium potentials for other, ions in the heart? 24

2.3.2 How do other ions contribute to the resting potential? 24

2.3.3 What is the influence of the Na⁺/K⁺ pump on the membrane potential? 29

2.3.4 What is the effect of changing extracellular [K⁺] on the membrane potential? 32

2.4 Summary 33

2.5 Questions 33

2.6 Bibliography 34

Chapter 3 Measuring Membrane Currents 35

3.1 Chapter objectives 35

3.2 Key electrical concepts: voltage, current, conductance and capacitance 36

3.2.1 Voltage 36

3.2.2 Current 36

3.2.3 Conductance 37

3.2.4 Capacitance 38

3.3 What is voltage clamp? 40

3.4 Hodgkin and Huxley experiments 43

3.4.1 Separating the early and late currents 46

3.4.2 Na⁺ and K⁺ channels conduct in a voltage- and time-dependent manner 47

3.4.3 Activation and inactivation of channels 48

3.5 Conclusions 53

3.6 Summary 56

3.7 Questions 58

3.8 Bibliography 59

3.8.1 Books and reviews 59

3.8.2 Original papers 60

Chapter 4 Channel Structure and Function 61

4.1 Chapter objectives 61

4.2 Ions flow through separate channels 61

4.3 Channels can be activated (or "gated") in various ways 62

4.4 Channels are specialized to allow the transport of specific ionic species 63

4.5 Channels can discriminate between ions 63

4.6 Channels can pass large ionic currents 63

4.7 Some channels can sense voltage 65

4.8 Biophysical techniques - the patch clamp 65

4.8.1 Ensemble currents 66

4.8.2 Other patch clamp configurations 70

4.9 Molecular techniques - working with frogs and fruit flies 72

4.9.1 Frogs 72

4.9.2 Fruit flies 73

4.10 Microscopy, electron diffraction and cryo-electron microscopy 75

4.11 More understanding of channel structure and function 76

4.12 Channel subunits 77

4.13 Channel structure 78

4.13.1 Protein structure - a recap 78

4.13.2 K⁺ channel structure 80

4.14 The structural basis of ion channel function 84

4.14.1 Sensing the voltage across the cell membrane 84

4.14.2 Moving ions into the channel 85

4.14.3 Discriminating between ions 88

4.15 Na⁺ channels 94

4.16 Channel inactivation 96

4.17 Other ways of altering channel function 99

4.18 Questions 99

4.19 Bibliography 100

4.19.1 Books and reviews 100

4.19.2 Original papers 100

Chapter 5 Active Transporters 105

5.1 Chapter objectives 105

5.2 What do active transporters do? 105

5.3 ATPases or pumps 106

5.3.1 Na⁺/K⁺ -ATPase 107

5.3.2 Na⁺/K⁺ pump isoforms 111

5.3.3 Na⁺K⁺ pump current and intracellular [Na⁺] 112

5.4 Ion exchangers 114

5.4.1 Na⁺/Ca²⁺exchanger 114

5.4.2 Na⁺/H⁺ exchanger 120

5.5 Interaction of ion transporters in the heart 122

5.5.1 The effect of alterations to intracellular [Na⁺] on contractile force 122

5.5.2 The effect of alterations to intracellular pH on contractile force 124

5.5.3 Interactions between H⁺ and Ca²⁺ 124

5.6 Summary 126

5.7 Questions 127

5.8 Bibliography 128

5.8.1 Reviews 128

5.8.2 Original papers 129

Chapter 6 Currents Flowing During the Early Part of the Ventricular Action Potential 131

6.1 Chapter objectives 131

6.2 Why describe the ventricular action potential? 132

6.3 The phases of the action potential 132

6.4 Phase 4 - Resting membrane potential 133

6.5 Phase 0 - the rapid upstroke (Na+ current) 134

6.5.1 Na⁺ channel inactivation and refractory periods 137

6.5.2 Channel nomenclature 140

6.5.3 Na_v1.5 140

6.5.4 The binding of TTX 141

6.5.5 The effect of local anaesthetics 141

6.5.6 Distribution of the Na⁺ channel 143

6.6 Phase 1 - Early repolarization 143

6.6.1 The transient outward current ? I₁₀ 144

6.7 Phase 1 - Ca²⁺ influx 151

6.7.1 The role of I_Ca,L 153

6.7.2 Ca²⁺ channels 158

6.7.3 Ca²⁺ channel structure 162

6.7.4 T-type Ca²⁺channels in the heart 172

6.8 Summary 173

6.9 Questions 175

6.10 Bibliography 176

6.10.1 Books and reviews 176

6.10.2 Original papers 177

Chapter 7 Currents Flowing During the Later Part of the Ventricular Action Potential 179

7.1 Chapter objectives 179

7.2 Phase 2 180

7.2.1 7_K1 180

7.3 Phase 2 continued 186

7.3.1 7_Kur 186

7.3.2 7_kr 189

7.3.3 7_Kr and hERG 191

7.3.4 7_Ks 197

7.3.5 Na⁺/Ca²⁺ exchange 201

7.3.6 I^{Na, late} 203

7.4 Phase 3 205

7.5 A summary of repolarizing currents 205

7.6 Questions 206

7.7 Bibliography 207

7.7.1 Reviews 207

7.7.2 Original papers 207

Chapter 8 Ionic Basis of Automaticity 209

8.1 Chapter objectives 209

8.2 The sino-atrial node 210

8.3 I_f 211

8.3.1 HCN channels 212

8.4 I_Ca,T 216

8.5 I_Ca,L 218

8.6 SR Ca²⁺ release in SA nodal cells 218

8.7 Potassium currents in the SA node 221

8.7.1 I_K,Ach 221

8.8 Cell heterogeneity 222

8.9 Summary 222

8.10 Questions 223

8.11 Bibliography 223

8.11.1 Reviews 223

8.11.2 Original papers 224

Chapter 9 Conduction, Arrhythmias and Anti-arrhythmic Agents 225

9.1 Chapter objectives 225

9.2 Simple conduction 225

9.3 Arrhythmias 233

9.3.1 Disturbances in impulse generation 233

9.3.2 Disturbances in impulse propagation 236

9.4 Anti-arrhythmics 240

9.4.1 Inhibiting Na⁺ channels 240

9.4.2 Inhibiting Ca²⁺ channels 242

9.4.3 Inhibiting K⁺ channels 244

9.4.4 Class II anti-arrhythmics 245

9.4.5 Other drugs 245

9.5 Summary 247

9.6 Questions 249

9.7 Bibliography 249

9.7.1 Books and reviews 249

9.7.2 Papers 249

Glossary 251

Answers to Chapter Questions 255

Index 265