Textbook of Ion Channels Volume III : Regulation, Physiology, and Diseases

TheTextbook of Ion Channels is a set of three volumes that provides a wide-ranging reference source on ion channels for students, instructors, and researchers. Ion channels are membrane proteins that control the electrical properties of neurons and cardiac cells, mediate the detection and response to sensory stimuli like light, sound, odor, and taste, and regulate the response to physical stimuli like temperature and pressure. In non-excitable tissues, ion channels are instrumental for the regulation of basic salt balance that is critical for homeostasis. Ion channels are located at the surface membrane of cells, giving them the unique ability to communicate with the environment, as well as the membrane of intracellular organelles, allowing them to regulate internal homeostasis. Ion channels are fundamentally important for human health and diseases, and are important targets for pharmaceuticals in mental illness, heart disease, anesthesia, pain and other clinical applications. The modern methods used in their study are powerful and diverse, ranging from single ion-channel measurement techniques to models of ion channel diseases in animals, and human clinical trials for ion channel drugs. Volume III includes coverage of key ion channel regulators and their mechanisms, the role of ion channels working in concert in selected physiological systems, and examples of ion channel mutations and dysfunction in a selection of diseases. Chapters on ion channel regulation include splice variants, calcium-calmodulin regulation, regulation by G-proteins, and lipids. A selection of ion channels in physiological systems includes ion channels of the heart, ion channels in immune cells and their role in pancreatic beta cells and regulation of insulin secretion, and the role of channels in sperm and eggs. While disease mechanisms are integrated into the chapters of Volume II, Volume III offers special consideration of ion channels in epilepsy, cystic fibrosis, and pain syndromes. All three volumes give the reader an introduction to fundamental concepts needed to understand the mechanism of ion channels, a guide to the technical aspects of ion channel research, offer a modern guide to the properties of major ion channel families, and include coverage of key examples of regulatory, physiological, and disease roles for ion channels. Cover Half Title Title Page Copyright Page Table of Contents Preface Editors Contributors Chapter 1 Alternative Splicing 1.1 Introduction 1.2 Gene Structure, Transcription and Protein Synthesis 1.3 Pre-mRNA Processing 1.3.1 The Spliceosome 1.3.2 RNA Editing 1.4 Alternative Splicing in Physiology 1.4.1 Species- or Tissue-Specific Splicing 1.4.2 Developmental Splicing 1.4.3 Activity- and Hormone-Dependent Splicing 1.4.4 Circadian Regulation of Splicing 1.4.5 Splicing and Disease 1.5 Summary Suggested Readings Chapter 2 Calmodulin Regulation of Ion Channels 2.1 Introduction 2.2 General Principles 2.3 CaV Channels 2.3.1 CaM as the Ca2+ Sensor for CDI 2.3.2 Functional Bipartition of Calmodulin and Selectivity for Local/Global Calcium Sources 2.3.3 Molecular Basis of CaM Regulation 2.3.4 Biological Consequences and Prospects for New Disease Therapies 2.4 NaV Channels 2.4.1 Ca2+-Dependent Regulation 2.4.2 Ca2+-Independent Regulation 2.5 TRP Channels 2.6 CaM Regulation of Potassium Channels 2.6.1 EAG 2.6.2 SK Channels 2.6.3 KCNQ (KV7) 2.7 Ryanodine Receptor (RyR) 2.8 NMDA Receptor 2.9 Disrupted Ca2+/CaM Regulation in Disease Suggested Readings Chapter 3 Regulation of G Protein-Gated Inwardly Rectifying K+ Channel Activity 3.1 Vagal Inhibition of Heart Rate 3.2 Molecular Components of KACh/GIRK Channel Regulation 3.2.1 GTP-Binding (G) Proteins and Their Signaling to KACh 3.2.2 GIRK Channel Cloning, Expression and Assembly 3.2.3 GIRK Channel Gating 3.3 Regulation of Activity by Posttranslational Modifications and Drugs 3.3.1 GIRK Channels as Drug Targets 3.4 Structural Insights 3.5 Future Questions Acknowledgments Suggested Readings Chapter 4 Regulation of Ion Channels by Membrane Lipids 4.1 Introduction 4.2 Composition of Biological Membranes 4.3 Glycerophospholipids 4.3.1 Neutral Phospholipids: PC and PE 4.3.2 Phosphatidylserine 4.3.3 PI and Phosphoinositides 4.3.3.1 PI(4,5)P2, the Master Regulator of Plasma Membrane Ion Channels, and Its Precursor PI(4)P 4.3.3.2 PI(3,4,5)P3 and PI(3,4)P2, the Products of PI3-Kinases in the Plasma Membrane 4.3.3.3 PI(3,5)P2, a Specific Cofactor for Intracellular Ion Channels 4.3.4 PG, Cardiolipin and Bacterial Ion Channels 4.4 Cholesterol 4.5 Sphingolipids 4.6 Conclusions and Future Perspective Suggested Readings Chapter 5 Ion Channels of the Heart 5.1 Generation of the Cardiac Action Potential and Excitation–Contraction Coupling 5.2 Cardiac Na Channel Physiology and Pathophysiology 5.2.1 Channel Structure and Function 5.2.2 Inherited and Acquired Cardiac Diseases 5.3 Cardiac L-Type Ca2+ Channel Physiology and Pathophysiology 5.4 Cardiac Ryanodine Receptors 5.4.1 Channel Function and Regulation 5.4.2 Inherited and Acquired Cardiac Diseases and RyR2 Function 5.5 Cardiac IP3 Receptors 5.6 Na+/Ca2+ Exchanger 5.7 Cardiac K+ Channels 5.7.1 Voltage-Gated K+ Channels 5.7.1.1 Transient Outward K+ Current 5.7.1.2 Delayed Rectifier K+ Current 5.7.2 Inwardly Rectifying K+ Channel 5.7.3 Ca2+-Activated K+ Channels 5.7.4 Transient Receptor Potential Channels 5.7.5 Two-Pore Domain K+ Channels 5.7.6 Funny Current If 5.8 Cardiac Cl– Channels 5.9 Triggered Arrhythmia and Cardiac Automaticity Suggested Readings Chapter 6 Ion Channels in Sperm and Eggs 6.1 Introduction 6.2 Sperm 6.2.1 Capacitation of Mammalian Sperm 6.2.2 Activation of Sperm from Aquatic Vertebrates 6.2.3 Chemotaxis 6.2.4 Acrosome Reaction 6.3 Fast Block to Polyspermy 6.3.1 Fast Block History 6.3.2 Fast Block in Frog Eggs 6.3.3 Fast Block in Sea Urchin Eggs 6.3.4 Depolarization Block of Sperm Entry 6.4 Ca2+ Events in the Egg at Fertilization 6.4.1 Ca2+ Oscillations in Mammalian Eggs 6.4.2 Fertilization-Signaled Ca2+ Events in Frog and Fish Eggs 6.4.3 Ca2+ Events in Drosophila Eggs 6.4.4 Ca2+ Signaling in Worm Eggs 6.4.5 Ca2+ Signaling in Plant Eggs 6.5 Conclusion Acknowledgments Suggested Readings Chapter 7 Ion Channels in Immune Cells 7.1 Introduction 7.2 Ion Channels in T Lymphocytes: Biophysical Fingerprint and Molecular Identification 7.2.1 Kv (Kv1.3) 7.2.2 KCa (KCa3.1 or KCa2.2) 7.2.3 Clswell, aka VRAC (LRRC8, aka Swell1) 7.2.4 CRAC (Orai1 and STIM1) 7.2.4.1 STIM Proteins in the ER: Dual Function as ER Ca2+ Sensor and CRAC Activator 7.2.4.2 Orai Channels in the Plasma Membrane: CRAC Pore 7.2.5 MIC (TRPM7) Channel-Kinase 7.2.6 Piezo 7.2.7 K2P, TRPM4, P2RX7 and Controversy Surrounding Voltage-Gated Ca2+ Channels 7.3 Adaptive Immunity and Cellular Homeostasis: Functional Networks of Ion Channels in T Cells 7.3.1 STIM1–Orai1, Kv1.3 and KCa3.1: Ca2+ Signaling 7.3.2 Ca2+ Regulation of Motility, Gene Expression and Metabolism 7.3.3 LRRC8C, Kv1.3, KCa3.1 and SWAC: Regulatory Volume Decrease (RVD) 7.3.4 Ion Channels in the Development and Differentiation of T Cell Subsets 7.3.5 Imaging T Cell Dynamics, Ca2+ Signaling, and Orai1 Channel Activity in vivo: Seeing Is Believing 7.3.6 Therapeutic Potential of Channel Blockers 7.4 Ion Channels in Neutrophils 7.4.1 HV 7.4.2 Anion Channels 7.4.3 P2RX7 Receptors 7.4.4 CRAC 7.5 Innate Immunity: Neutrophil Behavior during a Bacterial Infection 7.6 Ion Channel Phenotype and Function of Immune Cells 7.6.1 The Lymphoid Cell Lineage: Comparing Ion Channels in T Cells with B Cells and NK Cells 7.6.2 The Myeloid Cell Lineage: Comparing Ion Channels in Neutrophils with Other Granulocytes, Macrophages, Microglia, Dendritic Cells and Mast Cells 7.7 Concluding Remarks Acknowledgments Suggested Readings Chapter 8 Ion Channels in Epilepsy 8.1 Epilepsy Is a Dynamic Mesoscale Network Synchronization Disorder 8.2 Discovery of Pathogenic Ion Channels in Epilepsy 8.3 Ion Channel Subunit Mutations Are Only a Subset of Monogenic Epilepsies 8.4 Functional Characterization of Variants beyond the Pore 8.5 Inhibitory Microcircuits Are Major Functional Targets of Epileptic Channelopathies 8.6 Sodium Channels 8.7 Potassium Channels 8.8 Calcium- and Sodium-Activated Potassium Channels 8.9 Calcium Channels 8.10 HCN Channels 8.11 Cardiac Arrhythmia Ion Channels, Epilepsy and Sudden Death 8.12 Genes Altering Compartmental Channel Density 8.13 Homeostatic Current Nonlinearities in Developing Epileptic Brain 8.14 Channel-Based Therapy: Variant-Guided Clinical Management 8.15 Summary Suggested Readings Chapter 9 Ion Channels in Pain 9.1 Introduction 9.2 Pain Pathways 9.3 Nociceptive Neurons 9.4 Voltage-Gated Sodium Channels 9.5 NaV1.3 9.5.1 NaV1.3 Localization and Role in Nociceptor Signaling 9.5.2 NaV1.3 Biophysics 9.5.3 NaV1.3 in Sympathetic Neurons 9.5.4 Genetic Manipulation of NaV1.3 in Animal Pain Models 9.6 NaV1.7 9.6.1 NaV1.7 Localization and Role in Nociceptor Signaling 9.6.2 NaV1.7 Biophysics 9.6.3 NaV1.7 Human Genetics 9.6.4 NaV1.7 in Animal Pain Models 9.6.5 NaV1.7 and Opioid Pathways 9.6.6 NaV1.7 Pharmacology 9.7 NaV1.8 9.7.1 NaV1.8 Localization and Role in Nociceptor Signaling 9.7.2 NaV1.8 in Animal Pain Models 9.7.3 NaV1.8 Human Tissue Distribution and Genetic Data 9.7.4 NaV1.8 Pharmacology 9.8 NaV1.9 9.8.1 NaV1.9 Localization and Role in Nociceptor Signaling 9.8.2 NaV1.9 Biophysics 9.8.3 NaV1.9 in Animal Pain Models 9.8.4 NaV1.9 Human Genetics 9.9 Voltage-Gated KV7 Potassium Channels 9.9.1 KV7 Localization and Role in Nociceptor Signaling 9.9.2 KV7 in Animal Pain Models 9.9.3 KV7.2/7.3 Pharmacology 9.10 TRPV1 Channels 9.10.1 TRPV1 Localization and Role in Nociceptor Signaling 9.10.2 TRPV1 in Animal Pain Models 9.10.3 TRPV1 Pharmacology 9.11 CaV2.2 9.11.1 CaV2.2 Localization and Role in Nociceptor Signaling 9.11.2 CaV2.2 in Animal Pain Models 9.11.3 CaV2.2 Pharmacology 9.12 Other Channels Linked to Pain 9.13 Conclusions Suggested Readings Chapter 10 Cystic Fibrosis and the CFTR Anion Channels 10.1 Introduction 10.2 Brief History of Cystic Fibrosis 10.3 CFTR Overview 10.4 Regulatory Domain: Regulation of CFTR Activity by Phosphorylation 10.5 Nucleotide-Binding Domain: Gating Mechanism 10.6 Transmembrane Domain: Pore Properties and Anion Permeation 10.6.1 Lateral Entrance 10.6.2 Internal Vestibule 10.6.3 Narrow Region 10.6.4 External Vestibule 10.7 Molecular CF Pathophysiology and CFTR Pharmacology 10.7.1 Mutations That Lead to CF 10.7.2 Mechanism of CFTR Dysfunction 10.7.3 CFTR Pharmacology 10.8 Concluding Remarks Acknowledgments Suggested Readings Chapter 11 CLC-Related Proteins in Diseases 11.1 Introduction 11.2 ClC-1 11.2.1 Myotonia Congenita, Thomsen Disease (MIM 160800) 11.2.2 Recessive Generalized Myotonia, Becker Disease (MIM 255700) 11.2.3 Mechanism of Myotonia 11.2.4 Myotonic Dystrophy 1, Steinert Disease (MIM 160900), Myotonic Dystrophy 2, Proximal Myotonic Myopathy (PROMM), Ricker Syndrome (MIM 602668) 11.3 ClC-2 11.3.1 Leukoencephalopathies 11.3.2 Primary Aldosteronism 11.4 GlialCAM 11.5 ClC-Ka 11.6 ClC-Kb 11.6.1 Bartter Syndrome Type 3, Classic Bartter Syndrome (MIM 607364) 11.6.2 Gitelman Syndrome (MIM 263800), Gitelman-Like Syndrome 11.6.3 Bartter Syndrome Type 4B, Infantile Bartter Syndrome with Sensorineural Deafness (MIM 613090) 11.7 Barttin 11.8 ClC-3 11.9 ClC-4 11.10 ClC-5 11.11 ClC-6 11.12 ClC-7 11.12.1 Albers-Schönberg Disease, Autosomal Dominant Osteopetrosis 2 (MIM 166600); Infantile Malignant Osteopetrosis 2, Autosomal Recessive Osteopetrosis 4 (MIM 611490) 11.12.2 Syndrome with Cutaneous Albinism, Developmental Delay and Lysosomal Storage 11.13 Ostm1 (Infantile Malignant Osteopetrosis 3, Autosomal Recessive Osteopetrosis 5 [MIM 259720]) 11.14 Conclusions Acknowledgments Suggested Readings Chapter 12 KATP Channels and the Regulation of Insulin Secretion 12.1 Introduction 12.2 β-Cell Physiology 12.3 KATP Architecture 12.4 Nucleotide Modulation of KATP 12.5 Structure of the Nucleotide-Binding Sites of KATP 12.6 Nucleotide-Dependent Gating of KATP 12.7 Structural Basis of KATP Gating 12.8 Is ATP Hydrolysis at SUR1 Necessary for KATP Activation? 12.9 Physiological Response to Glucose 12.10 Other Modulators of KATP Gating 12.11 KATP Mutations That Affect Insulin Secretion 12.12 KATP Pharmacology and Insulin Secretion 12.13 Summary Suggested Readings Index The Textbook of Ion Channels is a set of three volumes that provides a wide-ranging reference source on ion channels for students, instructors and researchers. Ion channels are mem- brane proteins that control the electrical properties of neurons and cardiac cells; medi- ate the detection and response to sensory stimuli like light, sound, odor, and taste; and regulate the response to physical stimuli like temperature and pressure. In non-excitable tissues, ion channels are instrumental for the regulation of basic salt balance that is critical for homeostasis. Ion channels are located at the surface membrane of cells, giving them the unique ability to communicate with the environment, as well as the membrane of intracellular organelles, allowing them to regulate internal homeostasis. Ion channels are fundamentally important for human health and diseases, and are important targets for pharmaceuticals in mental illness, heart disease, anesthesia, pain and other clinical appli- cations. The modern methods used in their study are powerful and diverse, ranging from single ion-channel measurement techniques to models of ion channel diseases in animals, and human clinical trials for ion channel drugs.Volume III includes coverage of key ion channel regulators and their mechanisms, the role of ion channels working in concert in selected physiological systems, and examples of ion channel mutations and dysfunction in a selection of diseases. Chapters on ion channel regulation include splice variants, calcium–calmodulin regulation, regulation by G pro- teins, and lipids. A selection of ion channels in physiological systems includes ion chan- nels of the heart, ion channels in immune cells and their role in pancreatic beta cells and regulation of insulin secretion, and the role of channels in sperm and eggs. While disease mechanisms are integrated into the chapters of Volume II, Volume III offers special consid- eration of ion channels in epilepsy, cystic fibrosis and pain syndromes.All three volumes give the reader an introduction to fundamental concepts needed to understand the mechanism of ion channels, a guide to the technical aspects of ion channel research, offer a modern guide to the properties of major ion channel families, and includecoverage of key examples of regulatory, physiological, and disease roles for ion channels. This three-volume textbook provides a wide-ranging reference source on ion channels for students, instructors, and researchers. Volume III covers key ion channel regulators, the role of ion channels in selected physiological systems, and examples of mutations and dysfunction in selected diseases. G-protein;,Regulation;,Membrane,Lipids;,Heart;,Immune,Cells;,Pain;,Cystic,Fibrosis;,Proteins;,Diseases;,Calmodulin,Regulation;,Sperm,and,Eggs;,Ion,Channels;,Insulin;,CLC-Related,Proteins;,Epilepsy;,KATP,Channels;,Alternative,Splicing;,CFTR,Anion,Channels G-protein,Regulation,Membrane Lipids,Heart,Immune Cells,Pain,Cystic Fibrosis,Proteins,Diseases,Calmodulin Regulation,Sperm and Eggs,Ion Channels,Insulin,CLC-Related Proteins,Epilepsy,KATP Channels,Alternative Splicing,CFTR Anion Channels "From the editors of the renowned Handbook of Ion Channels, Textbook of Ion Channels is a student-friendly, advanced textbook that illustrates the fundamental importance of these membrane proteins to human health and disease. It has been split into three separate volumes so that each volume can target different needs. The basic concepts of ion channel research are introduced in the first volume, whilst volume two focuses on the pharmacology of ion channels' superfamilies, and volume three presents powerful methods for modeling ion channel diseases and performing clinical trials for ion channel drugs"-- Provided by publisher