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

Description

Pathological heart rhythms are a major health issue. In this book experts from various fields provide an important context for understanding the complicated molecular and cellular mechanisms that underlie normal and pathophysiological cardiac rhythms. Individual chapters cover a full range of topics, including the ionic basis of pacemaking, the role of specific channels and transporters in sinoatrial node pacemaking, altered intracellular Ca2+ handling in response to disease, computer modeling of the action potentials of pacemaker and working cardiomyocytes, genetic and molecular basis of inherited arrhythmias and a review of established and novel antiarrhythmic agents. Due to the key importance of the specialized pacemaker cells and tissue (sinoatrial and atrioventricular nodes) in maintaining heart rate and rhythm, special emphasis is placed on the peculiar electrophysiology of these cells. Front Matter....Pages i-xxii Front Matter....Pages 1-1 Cardiac Ion Channels and Heart Rate and Rhythm....Pages 3-31 Ionic Basis of the Pacemaker Activity of SA Node Revealed by the Lead Potential Analysis....Pages 33-58 The “Funny” Pacemaker Current....Pages 59-81 Novel Perspectives on Cardiac Pacemaker Regulation: Role of the Coupled Function of Sarcolemmal and Intracellular Proteins....Pages 83-99 Pacemaker Activity of the SA Node: Insights from Dynamic-Clamp Experiments....Pages 101-117 Heart Rate Variability: Molecular Mechanisms and Clinical Implications....Pages 119-132 Mechano-Electric Feedback in the Heart: Effects on Heart Rate and Rhythm....Pages 133-151 Front Matter....Pages 153-153 A Historical Perspective on the Development of Models of Rhythm in the Heart....Pages 155-173 Simulation of Cardiac Action Potentials....Pages 175-194 Front Matter....Pages 195-195 Development of Pacemaker Activity in Embryonic and Embryonic Stem Cell-Derived Cardiomyocytes....Pages 197-209 Molecular Basis of the Electrical Activity of the Atrioventricular Junction and Purkinje Fibres....Pages 211-230 Molecular Basis and Genetic Aspects of the Development of the Cardiac Chambers and Conduction System: Relevance to Heart Rhythm....Pages 231-253 Role of the T-Tubules in the Response of Cardiac Ventricular Myocytes to Inotropic Interventions....Pages 255-266 Front Matter....Pages 267-267 An Overview of Spiral- and Scroll-Wave Dynamics in Mathematical Models for Cardiac Tissue....Pages 269-282 Post-infarction Remodeling and Arrhythmogenesis: Molecular, Ionic, and Electrophysiological Substrates....Pages 283-304 The Role of Intracellular Ca 2+ in Arrhythmias in the Postmyocardial Infarction Heart....Pages 305-322 Molecular and Biochemical Characteristics of the Intracellular Ca 2+ Handling Proteins in the Heart....Pages 323-335 Pharmacological Modulation and Clinical Implications of Sarcolemmal Ca 2+ -Handling Proteins in Heart Function....Pages 337-349 Calmodulin Kinase II Regulation of Heart Rhythm and Disease....Pages 351-364 MicroRNA and Pluripotent Stem Cell-Based Heart Therapies: The Electrophysiological Perspective....Pages 365-383 Front Matter....Pages 385-385 Intracellular Calcium Handling and Inherited Arrhythmogenic Diseases....Pages 387-408 Molecular Mechanisms of Voltage-Gated Na + Channel Dysfunction in LQT3 Syndrome....Pages 409-429 The Short QT Syndrome....Pages 431-449 Adrenergic Regulation and Heritable Arrhythmias: Key Roles of the Slowly Activating Heart I Ks Potassium Channel....Pages 451-460 Defects in Ankyrin-Based Protein Targeting Pathways in Human Arrhythmia....Pages 461-472 Genetically Modified Mice: Useful Models to Study Cause and Effect of Cardiac Arrhythmias?....Pages 473-484 Genetics of Atrial Fibrillation....Pages 485-499 Front Matter....Pages 501-501 The Role of Gap Junctions in Impulse Propagation in the Heart: New Aspects of Arrhythmogenesis and New Antiarrhythmic Agents Targeting Gap Junctions....Pages 503-524 Possible Mechanisms of the Acute Ischemia-Induced Ventricular Arrhythmias: The Involvement of Gap Junctions....Pages 525-542 Role of NCX1 and NHE1 in Ventricular Arrhythmia....Pages 543-561 TRP Channels in Cardiac Arrhythmia: Their Role During Purinergic Activation Induced by Ischemia....Pages 563-579 Cardiac Aquaporins: Significance in Health and Disease....Pages 581-595 Front Matter....Pages 597-597 Ion Channels as New Drug Targets in Atrial Fibrillation....Pages 599-610 hERG1 Channel Blockers and Cardiac Arrhythmia....Pages 611-625 Preclinical Drug Safety and Cardiac Ion Channel Screening....Pages 627-638 QT Prolongation Is a Poor Predictor of Proarrhythmia Liability: Beyond QT Prolongation!....Pages 639-654 K Channel Openers as New Anti-arrhythmic Agents....Pages 655-668 Back Matter....Pages 669-678