Showing papers in "Comprehensive Physiology in 2002"

Electrical Heterogeneity in the Heart: Physiological, Pharmacological and Clinical Implications

Abstract: The sections in this article are: 1 Action Potential and Ionic Distinctions 1.1 Methodological Considerations in the Assessment of Electrical Heterogeneity 2 Pharmacological Distinctions 2.1 Epicardium versus Endocardium 2.2 M-cells versus Epicardium and Endocardium 2.3 M-Cells versus Purkinje Cells 3 Molecular Distinctions 3.1 Potassium Channels 3.2 Sodium Channels 3.3 Gap Junctions 3.4 Chloride Conductances 3.5 Calcium Channels 3.6 Pumps and Exchangers 4 Simulation of Action Potential Heterogeneity 5 Developmental Aspects 6 Physiological and Clinical Implications 6.1 Transmural Distribution of Ito and the J Wave 6.2 Phase 2 Re-entry as a Mechanism of Extrasystolic Activity 6.3 Phase 2 Re-entry as a Trigger for VT/VF: The Brugada Syndrome 6.4 Early Repolarization Syndrome 6.5 Ischemia 6.6 Role of Transmural Heterogeneity in Inscription of the Electrocardiographic T Wave 6.7 Role of Transmural Heterogeneity in Inscription of the U Wave 6.8 Role of Transmural Heterogeneity in the Long QT Syndrome 6.9 Torsade de Pointes 6.10 Pharmacological Therapy for LQTS: Reducing Transmural Dispersion of Repolarization 7 Summary

Modulation of Cardiac Myofilament Activity by Protein Phosphorylation

Abstract: The sections in this article are: 1 Modulation of Cardiac Myofilament Activity as A Physiological Regulatory Device 2 Major Functional Sarcomeric Proteins and the Transition from Diastole to Systole 2.1 Thin Filament Proteins in Diastole and Systole 2.2 Thick Filament Proteins in Diastole and Systole 2.3 Crossbridge and Thin Filament States in Diastole and in Systole 3 cTnI Function and Phosphorylation 3.1 Primary Structure of cTnI and Potential Sites of Phosphorylation 3.2 cTnI Protein Kinase A Sites 3.3 Functional Effects of Phosphorylation of cTnI by Protein Kinase A 3.4 cTnI Protein Kinase C Sites 3.5 Functional Effects of Phosphorylation of cTnI by Protein Kinase C 3.6 Integration of Signals for Cardiac Myocyte Hypertrophy/Failure with cTnI Protein Phosphorylation 4 cTnT Function and Phosphorylation 4.1 cTnT Primary Structure and Functional Domains 4.2 cTnT Sites of Phosphorylation 5 Tropomyosin Function and Phosphorylation 5.1 Tropomyosin isoforms and cardiac function 5.2 Tropomyosin Phosphorylation 6 MLC2 Function and Phosphorylation 6.1 Primary Structure of MLC2 and Functional Domains 6.2 Metal Binding to MLC2 6.3 MLC2 and Modulation of Striated Muscle Contraction 6.4 MLC2 Phosphorylation and Regulation of Crossbridges 7 Phosphorylation and Function of Cardiac Myosin Binding Protein C 7.1 Primary Structure of MyBP-C and Functional Domains 7.2 Phosphorylation Sites of Cardiac MyBP-C 8 Summary and Conclusions

Normal and Abnormal Conduction in the Heart

Abstract: The sections in this article are: 1 Basic Mechanisms of Cardiac Impulse Propagation 1.1 The Continuous Cable 1.2 Two-Dimensional Propagation and Wavefront Curvature 1.3 Structural Determinants of Anisotropic and Discontinuous Conduction 1.4 Propagation in Discontinuous Structures 1.5 Discontinuous Propagation in a Cell Chain and a Cell Strand 1.6 Anisotropic Propagation 1.7 The Electrical Resistance of the Extracellular Space 1.8 The Bidomain Behavior of Cardiac Tissue 2 The Activation of the Whole Heart—from the Sinus Node to the Ventricles 2.1 The Sinus Node—Spread of Excitation from the Sinus Node to the Atrium 3 Disturbances of Impulse Conduction and Conduction Block 3.1 The Safety Factor of Propagation 3.2 Effects of Changes in Resting Membrane Potential and Inhibition of Na+ Channels on Conduction Velocity 3.3 Conduction Slowing and Block: The Role of Ca++ Inward Current 3.4 Conduction Slowing and Discontinuous Conduction 3.5 Mechanisms of Unidirectional Block 4 Circulating Excitation, Re-Entry, and Spiral Waves 4.1 Anatomic Re-entry 4.2 Functional Re-entry—the Leading Circle Concept 4.3 Spiral Wave Re-entry 4.4 Transition from Functional to Anatomic Re-entry. Anchoring of Spiral Waves

Cellular Basis of Physiological and Pathological Myocardial Growth

Abstract: The sections in this article are: 1 Morphometric Analysis of Cell Size and Number in the Ventricular Myocardium 1.1 Myocyte Dimensional Properties and Number: Methodological Considerations 1.2 Confocal Microscopic Measurements of Myocyte Cell Volume 2 Morphometric Analysis of the Coronary Vasculature 3 Physiological Myocardial Growth: Maturation of the Heart 3.1 Ventricular Remodeling 3.2 Myocyte Adaptations 3.3 Cytoplasmic Adaptations in Myocytes 3.4 Capillary Adaptations 3.5 Conclusions 4 Aging of the Heart 4.1 Aging and Ventricular Remodeling 4.2 Aging and Myocyte Number 4.3 Aging and Myocyte Reactive Hypertrophy 4.4 Aging and the Coronary Arterial and Capillary Tree 4.5 Conclusions 5 Pressure and Volume Overload Hypertrophy 5.1 Cardiac Hypertrophy and Ventricular Remodeling 5.2 Cardiac Hypertrophy and Myocyte Size, Shape, and Number 5.3 Cardiac Hypertrophy and Volume Composition of Myocytes 5.4 Cardiac Hypertrophy and the Coronary Arterial and Capillary Tree 5.5 Conclusions 6 Ischemic Cardiomyopathy 6.1 Ischemic Cardiomyopathy and Ventricular Remodeling 6.2 Ischemic Cardiomyopathy, Myocyte Cell Loss, and Ventricular Function 6.3 Ischemic Cardiomyopathy and Myocyte Cellular Hypertrophy and Hyperplasia 6.4 Ischemic Cardiomyopathy and Volume Composition of Myocytes 6.5 Ischemic Cardiomyopathy and the Coronary Capillary Tree 6.6 Conclusions

Molecular Analysis of Voltage-Gated K+ Channel Diversity and Functioning in the Mammalian Heart

Abstract: The sections in this article are: 1 Electrophysiological Diversity of Voltage-Gated Myocardial K+ Channel Currents 1.1 Transient Outward K+ Current Channels, Ito 1.2 Delayed Rectifier K+ Currents, IK 1.3 Cellular/Regional Heterogeneity in Voltage-Gated K+ Current Expression and Properties 2 Molecular Determinants of Voltage-Gated Cardiac K+ Channels 2.1 Voltage-Gated K+ Channel Pore-Forming α Subunits 2.2 Accessory Subunits of Voltage-Gated K+ Channels 2.3 Voltage-Gated K+ Channels and the Cytoskeleton 3 Molecular Correlates of Functional Voltage-Gated K+ Channels 3.1 Molecular Genetics of Cardiac Delayed Rectifier K+ Currents, IKr and IKs 3.2 Transgenic and Targeted Gene Deletion Approaches 3.3 Molecular Correlates of Other Voltage-Gated Cardiac K+ Currents 4 Functional Consequences of in Vivo Alterations in Voltage-Gated Myocardial K+ Channels 4.1 QT Prolongation 4.2 Atrioventricular Block 4.3 Ventricular Arrhythmia/Tachycardia 4.4 Pathophysiology 5 Summary, Conclusions, and Future Directions

The Cardiac Ventricular Action Potential

Abstract: The sections in this article are: 1 Fundamental Principles 2 The Ventricular Cell is A Complex Interactive System 3 Ionic Basis of the Action Potential 3.1 The Normal Action Potential 3.2 The Premature Action Potential and Adaptation to Rate 4 Heterogeneity of Ventricular Action Potentials 5 Abnormal Repolarization. Example—Early Afterdepolarizations 6 Effects of Ionic Concentrations on the Action Potential. Example—Sodium Overload 7 Pathological Action Potential Changes. Example—Acute Ischemia 8 Epilogue

The Cardiac Na+‐Ca2+ Exchanger

Abstract: The sections in this article are: 1 A Brief Historical Perspective and Prelude to the Review 2 Physiological Role of The Cardiac Na+-Ca2+ Exchanger 3 Reverse Na+-Ca2+ Exchange as A Trigger for SR Ca2+ Release 4 Digitalis Effects 5 Immunolocalization 6 Transport Properties 6.1 Stoichiometry 6.2 Transport Mechanism 6.3 Turnover Rates and Exchanger Density 6.4 Ion Selectivity 6.5 Temperature Dependence 7 Molecular Biology of the Na+-Ca2+ Exchanger 7.1 The Prototypical Canine Cardiac Na+-Ca2+ Exchanger 7.2 The Exchanger Superfamily 7.3 Topology of the Na+-Ca2+ Exchanger 7.4 The Calx-α and Calx-β Repeats 7.5 Alternative Splicing of Na+-Ca2+ Exchangers 8 Regulation of Na+-Ca2+ Exchange 8.1 Ionic Regulation 8.2 Structure–Function Relationships of Ionic Regulation 8.3 Regulation by Phosphorylation 8.4 Regulation by PIP2 8.5 Regulation by pH 8.6 Cytoskeletal Interactions 9 Pharmacology of Na+-Ca2+ Exchange 9.1 The Exchanger Inhibitory Peptide, XIP 9.2 Other Peptide Inhibitors 9.3 KB-R7943 9.4 Other Inhibitors 10 Studies in Transgenic Mice 11 Adenoviral Transfection of Na+-Ca2+ Exchange Proteins 12 Antisense Oligonucleotides 13 Frequency-Dependent Behavior of Na+-Ca2+ Exchange 14 Developmental Changes 15 Species Differences 16 Pathophysiological Alterations in Na+-Ca2+ Exchange 16.1 Contribution of Na+-Ca2+ Exchange to Cardiac Injury 16.2 Alterations in Na+-Ca2+ Exchange Levels 17 Summary

Systolic and Diastolic Function (Mechanics) of the Intact Heart

Abstract: The sections in this article are: 1 Determinants of Systolic Function 1.1 Changes in Cardiac Shape and Dimensions 1.2 Performance of the Intact Ventricle Viewed from the Perspective of Isolated Muscle Function 1.3 The End-Systolic Pressure—Volume Relationship 1.4 Preload 1.5 Afterload 1.6 Contractility (Inotropic State) 1.7 Length-Dependent Activation 1.8 Strength-Interval Relations 1.9 Interaction Between Heart Rate and β-Adrenergic Stimulation 1.10 Mechanical Restitution and Postextrasystolic Potentiation 2 Assessing Contractility (Inotropic State) of the Heart 2.1 Acute Changes In Contractility 2.2 Methods Based on Changes in Ventricular Volumes and Dimensions in a Steady State 2.3 Methods Derived from Left Ventricular Pressure and the Rate of Change of Pressure 2.4 Comparison of Indices 2.5 Methods Based on Examination of Ventricular Function over a Range of Loading Conditions 2.6 The Absolute Level of Inotropic State 2.7 Evaluation of Ventricular Function in Mice and Rats 3 Regional Function 3.1 Regional Right Ventricular Systolic Function 3.2 Regional Left Ventricular Structure-Function Relationships 3.3 Left Ventricular Structure-Function Relationships 3.4 Mechanical Correlates of Cardiac Energy Consumption 4 Determinants of Diastolic Function 4.1 Cardiac Structural Components 4.2 Passive Pressure-Volume Relationships 4.3 Time-Dependent Properties 4.4 Passive Ventricular Diastolic Structure-Function Relationships 4.5 Regulation of Ventricular Filling 4.6 Role of the Pericardium

Gap Junctions in the Cardiovascular System

Abstract: The sections in this article are: 1 Cardiovascular Gap Junction Proteins 11 Ultrastructural Features 12 Higher Resolution Through Projection Images 13 The Connexin Multigene Family 14 Connexin and Connexon Topology 15 Regional Connexin Expression in the Cardiovascular System 16 Why Are There Multiple Cardiovascular Connexins? 2 Macroscopic Organization of the Heart (Cables, Bricks, and Textures) 21 Gap Junction Organization within the Tissue 22 Modeling Tissue Connections 23 Optical Imaging of Patterned Cell Cultures 24 Microscopic and Macroscopic Discontinuities 3 Regulation of Gap Junction Expression, Formation, and Degradation 31 Life and Death of Gap Junctions 32 Long-Term Changes in Gap Junction Expression 33 Transcriptional Regulation of Cardiac Gap Junction Genes 4 Functional Properties of Cardiovascular Gap Junctions 41 Cardiovascular Gap Junctions Are K+, Ca2+, and Second Messenger Channels 42 Biophysical Properties of Junctional Channels 43 Gating of Gap Junctional Channels by Transjunctional Voltage 44 Properties of Specific Connexins Expressed in Exogenous Systems 45 Properties of Gap Junctions Evaluated in Cardiovascular Cells 46 Gating of Gap Junctions by Other Stimuli 5 Genetic and Somatic Disease States in Which Gap Junction Expression or Function is Altered 51 Somatic Cardiac Abnormalities 52 Reversed Physiology: Inferring Gene Function from Its Absence in Knockout Mice

Cardiac Sarcoplasmic Reticulum Ca2+‐ATPase

Abstract: The sections in this article are: 1 Structure of the Ca2+-ATPase 1.1 Structure of Cardiac Sarcoplasmic Reticulum 1.2 Isolation and Characterization of Cardiac Sarcoplasmic Reticulum 2 Function of Ca2+-ATPase 2.1 Ca2+ Pumping Function 2.2 Mechanism of Ca2+-ATPase Activity 2.3 Regulation of Ca2+-ATPase Activity 3 Structure and Function of Ca2+-ATPase 3.1 Primary Sequences and Structural Models for Ca2+-ATPases 3.2 Chemical Modifications of the Ca2+-ATPase 3.3 Site-Directed Mutagenesis of Ca2+-ATPase 3.4 Ca2+-ATPase Isoform Chimeras 4 Regulation of Ca2+-ATPase by Phospholamban 4.1 Structure of Phospholamban 4.2 Function of Phospholamban 4.3 Interaction Between Ca2+-ATPase and Phospholamban 4.4 Physiological Relevance of Phospholamban-Ca2+-ATPase System 5 Regulation of Ca2+-ATPase and Phospholamban Genes 5.1 Structure of the Ca2+-ATPase Gene 5.2 Transcriptional Regulation of the Ca2+-ATPase Gene 5.3 Structure of the Phospholamban Gene 5.4 Transcriptional Regulation of the Phospholamban Gene

Vagal Preganglionic Neurons Innervating the Heart

Abstract: The sections in this article are: 1 Chronotropic Actions of Activating Vagal Efferent Fibers 2 B-Fibers and C-Fibers: Effect of Electrical Stimulation 3 The Location of the Somata of Preganglionic Vagal Neurons 4 Physiological Mapping 5 Biophysical Properties of Cardiac Vagal Motoneurons 6 Physiological Properties of Cardiac Vagal Motoneurons 7 Baroreceptor Input 8 Respiratory Influences on Cardiac Vagal Motoneuron Discharge 9 Mechanisms of Respiratory Patterning 10 Arterial Chemoreceptor Inputs 11 Pulmonary and Airway Inputs 11.1 Slowly Adapting Pulmonary Inputs 11.2 Rapidly Adapting Pulmonary Inputs 12 Pulmonary C-Fibers 13 Upper Airway Receptors 14 Cardiac Receptors 15 CNS Organization of Reflex Control 16 CNS Pathways Impinging on the Dorsal Ventral Nucleus and the Nucleus Ambiguus 17 Reflex Interactions: CNS Organization 18 Synaptic Effects Elicited by Baroreceptor Inputs in the Nucleus Tractus Solitarii 19 Synaptic Effects of Arterial Chemoreceptor Inputs 20 Central Modifications of Reflex Function 21 The Role of the Nucleus Tractus Solitarii in Reflex Adjustments 22 Respiratory Influences of Reflex Transmission Through the Nucleus Tractus Solitarius 23 Conclusions

Ultrastructure of the Heart

Abstract: The sections in this article are: 1 Shape, Motion, and Force Vectors 2 The Extracellular Matrix 2.1 Collagen Weave 2.2 Transverse (T)-Tubules 3 Interior Supporting Networks 3.1 Microtubules 3.2 Intermediate Filament Network 3.3 Sarcolemmal Associations 3.4 Titin Filament Network 4 The Myofilament Bundles and Associated Structures 5 The Dynamic Z-Band Lattice 5.1 Contractile and Elastic Components in Relation to the Z-Band 5.2 Protein Composition 5.3 Perturbed States of the Z-Band 5.4 Functional States of the Z-Band 6 Summary

Regulation of Cardiac Contraction by Calcium

Abstract: The sections in this article are: 1 Contractile and Regulatory Proteins of the Cardiac Myofibril 11 Myosin 12 Actin 13 Troponin 14 Tropomyosin 15 C-Protein 2 Mechanical Properties of Myocardium 21 Isometric Tension 22 Shortening Velocity 23 Tension Transients 3 Regulation of Myocardial Contraction 31 Tension 32 Shortening Velocity 33 Kinetics of Tension Development and Relaxation 4 Conclusions

Regulation of Cellular Calcium in Cardiac Myocytes

Abstract: The sections in this article are: 1 General Aspects of Cellular Calcium Regulation 1.1 Ca Transport Systems 1.2 Cytosolic Volume Conventions 1.3 Ca Binding Sites and Buffering in Cardiac Myocytes 1.4 Ca Requirements for Contractile Activation 1.5 Simplified Kinetic Considerations During a Ca Transient 2 Sarcolemmal Ca Transport Systems 2.1 Ca Channels 2.2 Na/Ca Exchange 2.3 Sarcolemmal Ca-ATPase 3 Intracellular Ca Transporters 3.1 Sarcoplasmic Reticulum Ca-ATPase and Sarcoplasmic Reticulum Ca Content 3.2 Sarcoplasmic Reticulum Ca Release Channels 3.3 Mitochondrial Ca Transport 4 Ca Removal from the Cytoplasm During Relaxation 4.1 Relative Contributions of Ca Transporters 4.2 Species, Developmental, and Temperature Dependence 4.3 Ca Recycling from Mitochondria Back to the SR 5 The Ca Supply that Activates Contraction 5.1 Ca Influx vs SR Ca Release 5.2 Fraction of SR Ca Released During a Twitch 6 Perturbations of Cellular Ca Balance 6.1 Rest-Dependent Changes in Cellular and SR Ca Content 6.2 Refilling Depleted Internal Ca Stores 6.3 Rest-Decay and Rest-Potentiation of Twitches 6.4 Force-Frequency Relationships

Cell Physiology and Cell Biology of Myocardial Cell Caveolae

Abstract: The sections in this article are: 1 Caveolae 2 Ultrastructure 3 Morphometric Studies 4 Accessibility of the Lumens of Caveolae to Extracellular Macromolecules 5 Opening and Closure of Cardiac Myocyte Caveolae 6 Reversible Changes in Myocardial Cell Caveolar Volume and Surface Density in Hypertonic Solutions 7 Hypertonic Solutions Increase Mean Caveolar Neck Surface Density and Diameter 8 Water-Channel Proteins in Mammalian Cardiac Myocytes 9 Temperature Dependence of the Co-Localization of Aquaporin-1 With Caveolin3 10 Physiological Role of Aquaporin-1 in Human Cardiac Myocyte Caveolae 11 Relationship of Atrial Myocyte Caveolae to Atrial Granules 12 Localization of the Type B Atrial Natriuretic Peptide Receptor in Atrial Myocyte Caveolae 13 Co-Localization of Endothelium-Derived Nitric Oxide Synthase With Caveolin3 in Rat Cardiac Myocyte Caveolae 14 Endothelin and Protein Kinase C Isoforms in Cardiac Myocyte Caveolae 15 Immunoelectron Microscopic Localization of the Monocarboxylate Transporter, MCT-1 in in Situ Rat Left Ventricular Myocytes 16 Neuregulin Binding to its Receptor in Cardiac Myocyte Caveolae 17 Adenosine A1 Receptor in Adult Cardiac Ventricular Myocytes 18 Exploration of Possible Interactions of Cardiac Myocyte Caveolae With Extracellular Matrix and Cytoskeleton-Associated Proteins: Dystrophin and Dystroglycan 19 Dynamic Clustering of Sphingolipids and Cholesterol to form Functional “Rafts” in Cellular Membranes 20 Development of More Efficient, Specific, and Sensitive Methods for Identifying the Intracaveolar and Caveolae-Bound Proteins of Cardiac Myocytes 21 Selected General Topics in Caveolar or Caveolae-Relevant Biology 21.1 Physical considerations—caveolae as plasma membrane microdomains or plasma membrane-associated microdomains 21.2 Caveolar Proteins 21.3 Other Caveolar Proteins: Reality vs. Artifact

Modulation of Electrical Properties by Ions, Hormones, and Drugs

Abstract: The sections in this article are: 1 Effects of Electrolytes 1.1 Potassium Ions 1.2 Sodium Ions 1.3 Calcium and Other Divalent Cations 1.4 Chloride Ions 2 Effects of pH and Physical Factors 2.1 pH 2.2 Temperature 2.3 Stretch and Osmotic Pressure 3 Effects of Neurohormones and Their Receptor Stimulations 3.1 Adrenoceptor Agonists and Adrenergic Receptor Stimulation 3.2 Cholinergic Agonists and Cholinergic Receptor Stimulation 4 Effects of Circulatory Hormones and Autocrine/Paracrine Substances 4.1 Thyroid Hormones and Thyroid States 4.2 Insulin and Diabetes Mellitus 4.3 Effects of Adenosine and Adenine Nucleotides Through Purinergic Receptor Stimulation 4.4 Histamine and Histamine H2 Receptor Stimulation 4.5 Angiotensin II and Angiotensin Receptor Stimulation 4.6 Arginine Vasopressin and Vasopressinergic Receptor Stimulation 4.7 Endothelins 4.8 Atrial Natriuretic Peptide 4.9 Nitric Oxide 5 Effects of Drugs 5.1 Digitalis Glucosides 5.2 Potassium Channel Openers

Newly Cloned Threshold Channels

Abstract: The sections in this article are: 1 The Pacemaker Current (If, Ih, or HCN) 2 Molecular Cloning 3 Structure of HCN Channels 4 Distribution Patterns of HCN Genes 5 Biophysical Properties of HCN Channels 6 Low-Voltage Activated Calcium Channels 7 Molecular Cloning and Distribution 8 Structure 9 Biophysics 9.1 Comparison of α1G, α1H, and α1I 9.2 How Voltage Dependent Are T-type Calcium Channels? 9.3 Selectivity and Block of T-Type Calcium Channels 10 Summary

Kinetics of the Actin–Myosin Interaction

Abstract: The sections in this article are: 1 Crossbridges and Sliding Filaments 2 Regulation 3 Myosin and Actomyosin ATPase 3.1 Rates of Specific Steps 3.2 Energetics of Specific Steps 3.3 Cardiac versus Skeletal Actomyosin ATPase 4 The Crossbridge Cycle in Muscle 4.1 Energy Transduction and Muscle Mechanics 4.2 Transient Kinetics in Fibers Using Caged Compounds 4.3 Analysis of Specific Steps 4.4 Cardiac Muscle 5 In Vitro Motility 6 Atomic Structures of Actin and Myosin 6.1 Myosin S1 6.2 Actomyosin 6.3 Comparison of Structural Models to Other Models 7 Recent Progress 8 Regulation 8.1 The Steric Blocking Model 8.2 Kinetic Regulation 8.3 Dual Regulation of the Crossbridge Cycle 8.4 Phosphorylation and Protein Isoform Switching 9 Summary and Concluding Comments

Ion Channels in the Heart: Cellular and Molecular Properties of Cardiac Na, Ca, and K Channels

Abstract: The sections in this article are: 1 Calcium Channels 2 Sodium Channels 2.1 Primary Structure of the Voltage-Gated Na+ Channel 2.2 Molecular Pharmacology of Na+ Channels 2.3 Molecular Pharmacology of an Inherited Disease 3 Potassium Channels 3.1 Voltage-Dependent K+ Channels 3.2 Inward Rectifier K Channels 4 Summary

A Modern View of Heart Failure: Practical Applications of Cardiovascular Physiology

Abstract: The sections in this article are: 1 Paradigmatic Shifts 2 Definition of Heart Failure 3 The Paradigm of Organ Physiology: The Failing Heart as a Defective Pump 3.1 Backward and Forward Failure 3.2 Systolic and Diastolic Dysfunction 3.3 Right and Left Heart Failure 3.4 The Neurohumoral Response in Heart Failure 3.5 Crossover Between Functional and Proliferative Signaling 3.6 Coupling Between the Failing Heart and the Circulation: Pressure–Volume Loops 3.7 Architectural Changes in the Failing Heart 4 The Paradigm of Biochemistry and Biophysics: The Failing Heart as a Weakly Contracting, Incompletely Relaxing Muscle 4.1 Inotropic and Lusitropic Abnormalities 4.2 Energy-Starvation 4.3 Molecular Alterations and Architectural Changes 5 The Paradigm of Gene Expression: The Failing Heart as an Abnormal Molecular Structure 5.1 Adaptive and Maladaptive Hypertrophy 5.2 Cardiac Myocyte Phenotypes 5.3 Shape Changes in the Cells of the Overloaded Heart 5.4 Myocardial Cell Death 6 Summary and Conclusions

Ion Channels and Cardiac Arrhythmia in Heart Disease

Abstract: The sections in this article are: 1 Background 1.1 The Clinical Problem—Tachyrhythmia in Structural Heart Disease 1.2 Arrythmia and Mechanisms 1.3 Currents Underlying the Action Potential 1.4 The Role of Ion Channels in Arrhythmia 2 Electrophysiology of Acquired Heart Disease 2.1 Human and Animal Models for Cellular and Molecular Electrophysiology 2.2 Specific Cellular Electrophysiological Changes in Acquired Heart Disease 3 Ion Channel Changes in Acquired Heart Disease 3.1 General Considerations 3.2 Specific Ion Currents and Arrhythmia 3.3 Summary of Electrical Remodeling in Acquired Heart Disease 4 The Long Q-T Syndrome 4.1 Introduction 4.2 Arrhythmic Mechanism 4.3 Molecular Mechanisms 4.4 Implications for Therapy 4.5 Present Status 5 Idiopathic Ventricular Fibrillation 6 Inherited Cardiomyopathy 6.1 Introduction 6.2 Clinical Picture 6.3 Arrhythmic Mechanisms