Cardiac Mechanotransduction Book

Preface xi

1 The Mechanosensory Heart: A Multidisciplinary Approach Matti Weckstrom Pasi Tavi 1

Introduction: Mechanosensation in the Heart 1

Cornucopia of Cardiac Mechanotransduction 4

2 Origin of Mechanotransduction: Stretch-Activated Ion Channels Clive M. Baumgarten 8

Terminology 9

How Are Mechanical Forces Transmitted in the Heart? 10

Characteristics of Mechanosensitive Currents in Single Channel Recordings 11

Characteristics of Mechanosensitive Currents in Whole-Cell Recordings 15

Effects of Stretch on Cardiac Electrical Activity 19

Stretch-Induced Elevation of [Ca2+]i and [Na+]i 20

3 The Role of the Sarcomere and Cytoskeleton in Cardiac Mechanotransduction Sarah C. Calaghan Ed White 28

The Sarcomere and Force Development 29

The Cytoskeleton and Mechanotransduction 38

4 Mechanoelectric Transduction/Feedback Physiology and Pathophysiology Max J. Lab 48

Brief Historical Introduction 48

Prevalence 49

Some Pitfalls in Interpretation 53

Mechanisms: Mechanoelectric Transducers as the Initiating Event 54

Theoretical (Abstract) Reflections 57

Pathophysiology: Clinically Related Expression 61

Mechanoelectric Transduction/Feedback as a Fundamental Surrogate in Arhythmia? 61

5 Mechanotransduction in Cardiac Remodeling and Heart Failure Jeffrey H. Omens Andrew D. McCulloch Ilka Lorenzen-Schmidt 78

Introduction: Cardiac Remodeling and Failure Are Dependent on Mechanical Forces 78

Myocyte Response to External Loads 79

Mechanotransduction 81

The Cytoskeleton and Its Role in Load Transduction 82

LIM Protein Deficiencies Lead to Cardiomyopathies 83

6 Second Messenger Systems Involved in Heart Mechanotranduction HiroshiHasegawa Hiroyuki Tankano Yunzeng Zou Hiroshi Akazawa Issei Komuro 93

Neurohumoral Factors Mediate Mechanical Stress-Induced Cardiac Hypertrophy 94

The Mitogen-Activated Protein (MAP) Kinase Pathway 96

The JAK/STAT Pathway 96

ECM-Integrin Pathway 97

Ca2+ Regulates the Development of Cardiac Hypertrophy 97

7 The Role of Adrenoceptors in Mechanotransduction Klaus-Dieter Schluitter Hans Michael Piper Sibylle Wenzel 106

Adrenoceptors in the Heart 107

The Role of α1-Adrenoceptors in Pressure Induced Hypertrophy 107

α1-Adrenoceptors and Their Involvement in Pressure Induced Hypertrophy 108

The Signalling of α1-Adrenoceptors in Pressure Induced Hypertrophy 109

The Role of α2-Adrenoceptors in Pressure Induced Hypertrophy 111

The Role of β1-Adrenoceptors in Pressure Induced Hypertrophy 111

The Role of β2-Adrenoceptors in Pressure Induced Hypertrophy 113

8 Intracellular Signaling Through Protein Kinases in Cardiac Mechanotransduction Peter H. Sugden 120

'Extrinsic' and 'Intrinsic' Mechanotransduction 121

Endpoints of Myocyte and Myocardial Hypertrophy 121

Signaling in Mechanotransduction and Hypertrophy: Protein Kinase C 122

Signaling in Mechanotransduction and Hypertrophy: The Extracellular Signal-Regulated Kinases 1/2 Cascade 124

Signaling in Mechanotransduction and Hypertrophy: The Strees-Activated Protein Kinases 126

'Focal Adhesion'-Associated Signaling: Basic Information 127

Signaling in Mechanotransduction and Hypertrophy: Focal Adhesion-Based Signaling 128

Signaling in Mechanotransduction and Hypertrophy: Other Protein Kinases (and Phosphatases) 128

9 Mechanotransduction of the Endocrine Heart Paracrine and Intracellular Regulation of B-Type Natriuretic Peptide Synthesis Sampsa Pikkarainen Heikkie Tokola Heikki Ruskoaho 134

Natriuretic Peptide Family 134

Activation of BNP Synthesis by Mechanical Load 135

Local Paracrine and Autocrine Factors and BNP Synthesis during Mechanical Load 136

Cytosolic Mechanotransduction on BNP Gene 137

Nuclear Mechanotransduction on BNP Gene 139

Index 145