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 II starts with ion channel taxonomy and features coverage of major ion channel families and describes the physiological role, structural components, gating mechanisms and biophysics, permeation and selectivity, regulation, pharmacology and roles in disease mechanisms. Channels in this volume include voltage-activated sodium, calcium and potassium channels, inward-rectifier and two-pore domain potassium channels, calcium-activated potassium channels, cyclic-nucleotide gated channels, pacemaker ion channels, chloride channels, the ligand-gated receptors activated by acetylcholine, glutamate, 5-HT3, GABA and glycine, acid-sensing channels, P2X receptors, TRP channels, store-operated channels, pressure-activated piezo channels, ryanodine receptors and proton channels.
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.
Author(s): Jie Zheng, Matthew C. Trudeau
Publisher: CRC Press
Year: 2023
Language: English
Pages: 488
City: Boca Raton
Cover
Half Title
Title Page
Copyright Page
Table of Contents
Preface
Editors
Contributors
Chapter 1 Taxonomy and Evolution of Ion Channels
1.1 How Should We Approach Ion Channel Taxonomy?
1.2 Ion Channel Superfamilies Have Independent Evolutionary Origins
1.3 Structural Diversification of the Voltage-Gated Cation Channel (VGIC) Superfamily
1.4 Ion Channel Families and Subfamilies
1.5 Evolutionary History of Ion Channels: Ancient Structures and Dynamic Gene Sets
1.6 Much of the Genetic Diversity of Ion Channels Remains Unexplored
Suggested Reading
Chapter 2 Voltage-Gated Sodium Channels
2.1 Functional Roles of Voltage-Gated Sodium Channels
2.1.1 Action Potential Generation and Propagation
2.1.2 Activation, Conductance and Two Phases of Inactivation
2.1.3 Persistent and Resurgent Sodium Currents
2.2 Discovery and Biochemical Properties of the Sodium Channel Protein
2.2.1 Identification, Purification and Reconstitution of Sodium Channels
2.2.2 Primary Structures of Sodium Channel Subunits
2.2.3 Mapping the Molecular Components Required for Sodium Channel Function
2.3 Three-Dimensional Structure of the Sodium Channel
2.3.1 Structure of Bacterial Sodium Channels
2.3.2 The Pore Contains a High-Field-Strength Carboxyl Site and Two Carbonyl Sites
2.3.3 Voltage-Sensor Structure
2.3.4 Voltage-Dependent Activation Involves a Sliding-Helix Mechanism
2.3.5 An Iris-Like Movement Opens the Pore
2.4 The Pore Collapses during Slow Inactivation
2.5 Drugs Block the Pores of Sodium Channels
2.6 Evolutionary Additions to Mammalian Sodium Channels
2.7 Sodium Channel Diversity
Suggested Reading
Chapter 3 Voltage-Gated Calcium Channels
3.1 Introduction
3.2 VGCC Diversity, Nomenclature and Structural Organization
3.3 Physiological Roles of VGCCs
3.4 Gating of VGCCs
3.5 Ion Permeability of VGCCs
3.6 Pharmacology of VGCCs
3.7 Regulation of VGCCs
3.8 Biogenesis, Trafficking and Turnover of VGCCs
3.9 VGCC Channelopathies and Disease
3.10 Conclusion
Suggested Reading
Chapter 4 Voltage-Gated Potassium Channels
4.1 Introduction
4.2 Structure of Kv Channels
4.3 The Pore Domain
4.4 Ionic Selectivity and Permeation
4.5 Voltage-Sensor Domains and the Mechanism of Voltage Gating
4.6 N-Type and C-Type Inactivation
4.7 Kv Channel Families
4.7.1 The Kv1 Family
4.7.2 The Kv2 Family
4.7.3 The Kv3 Family
4.7.4 The Kv4 Family
4.7.5 Kv5, Kv6, Kv8 and Kv
4.8 Pharmacology of Kv Channels
4.9 Kv Channel Accessory Proteins
4.10 Biogenesis of Kv Channels
4.11 Unresolved Questions and Research Directions
Acknowledgments
Suggested Reading
Chapter 5 ERG Family of Potassium Channels
5.1 Introduction
5.2 Physiological Roles
5.3 Subunit Diversity and Basic Structural Organization
5.4 Channel Physiology and Gating Mechanisms
5.4.1 Physiology
5.4.1.1 ERG
5.4.1.2 EAG
5.4.1.3 ELK
5.4.2 Gating Mechanisms
5.4.2.1 ERG
5.4.2.2 EAG
5.4.2.3 ELK
5.5 Ion Permeability
5.6 Regulation
5.7 Cell Biology (Biogenesis, Trafficking, Turnover)
5.8 Channelopathies and Disease
5.9 Pharmacology
5.9.1 hERG, IKr and Acquired LQTS
5.10 Conclusion
Suggested Reading
Chapter 6 KCNQ Channels
6.1 Introduction
6.2 Physiological Roles
6.3 Channel Diversity/Structural Organization
6.4 Gating
6.5 Ion Permeability
6.6 Pharmacology
6.7 Regulation
6.8 Cell Biology (Biogenesis and Trafficking)
6.9 Channelopathies
6.10 Conclusions
Suggested Reading
Chapter 7 BK channels
7.1 Functional Properties of BK Channels
7.2 Physiological Roles of BK Channels
7.3 BK Channel Structure
7.4 Allosteric Mechanisms of BK Channel Activation
7.5 Structural Basis of BK Channel Function
7.5.1 Large Single-Channel Conductance
7.5.2 Voltage- and Ca2+-Dependent Activation
7.5.3 Activation by Other Intracellular Ions
7.6 β and γ Subunits Modulate BK Channel Function
7.7 Pharmacology of BK Channels
7.8 Concluding Remarks
Acknowledgments
Suggested Reading
Chapter 8 Small-Conductance Calcium-Activated Potassium (SK) Channels
8.1 Introduction
8.2 Physiological Function
8.3 Subunit Diversity and Structure
8.4 Gating and Ion Permeability
8.5 Pharmacology
8.6 Regulation
8.7 Cell Biology (Biogenesis, Trafficking, Turnover)
8.8 Channelopathies and Disease
8.9 Conclusions
Suggested Reading
Chapter 9 Inward Rectifier Potassium Channels
9.1 Introduction
9.2 Physiological Roles
9.3 Subunit Diversity and Basic Structural Organization
9.4 Gating of Kir Channels
9.4.1 Regulators of Kir Channel Gating
9.4.2 Conformational Changes during Kir Channel Gating
9.5 Ion Selectivity and Conduction
9.6 Pharmacology
9.6.1 Peptide Toxins
9.7 Regulation
9.8 Cell Biology: Biogenesis, Trafficking, Subcellular Targeting
9.9 Kir Channelopathies
9.10 Conclusion
Acknowledgments
Suggested Reading
Chapter 10 Two-Pore-Domain Potassium Channels
10.1 Introduction to the Physiology of K2P Channels
10.2 Structural Organization and Subunit Diversity
10.3 Gating K2P Channels
10.4 The Regulation and Cell Biology of the K2P Channels
10.4.1 K2P1, K2P6 and K2P7 Channels
10.4.2 K2P2, K2P4 and K2P10 Channels: Polymodal Rheostats
10.4.3 The Acid-Sensitive Channels: K2P3 and K2P
10.4.4 Alkaline-Activated Channels: K2P5, K2P16 and K2P17
10.4.5 K2P12 and K2P13 Channels
10.4.6 K2P18 Channels and the Pathophysiology of Pain
10.5 Pharmacology and Emerging Perspectives on the Role of K2P Channels in Pathophysiology
10.6 Conclusions
Suggested Reading
Chapter 11 Cyclic Nucleotide-Gated Channels
11.1 Introduction
11.2 Physiological Roles of CNG Channels
11.3 CNG Channel Subunit Diversity and Structural Organization
11.4 Gating of CNG Channels
11.4.1 Ligand Binding at CNBD
11.4.2 Gating Conformational Changes through C-Linker Module to Pore Gate of CNG Channels
11.4.3 CNG Channel Activation Schemes and Subunit Contributions
11.5 Pore Properties of CNG Channels
11.6 Pharmacology of CNG Channels
11.7 Regulation of CNG Channels
11.8 CNG Channel Cell Biology
11.9 CNG Channel Disease Mechanisms
11.10 Conclusions
Suggested Reading
Chapter 12 HCN Channels
12.1 Introduction
12.2 Basic Structural Organization and Subunit Diversity
12.3 Gating
12.4 Ion Permeability
12.5 Regulation and Cell Biology
12.6 Pharmacology
12.7 Physiological Roles
12.7.1 Cardiac Pacemaking
12.7.2 HCN Channel Function in the Nervous System
12.8 Channelopathies, Disease, and Therapeutic Opportunities
12.9 Conclusions
Suggested Reading
Chapter 13 CLC Chloride Channels and Transporters
13.1 Introduction
13.2 Physiological Roles
13.2.1 CLC Channels
13.2.2 CLC Transporters
13.3 Subunit Diversity and Basic Structural Organization
13.4 Gating
13.4.1 CLC Channels
13.4.2 CLC Transporters
13.5 Ion Permeability
13.6 Pharmacology
13.7 Regulation
13.8 Cell Biology
13.9 Channelopathies and Disease
13.10 Conclusions
Acknowledgments
Suggested Reading
Chapter 14 Calcium-Activated Cl– Channels
14.1 Introduction
14.2 Physiological Roles
14.3 Tmem16/Anoctamin Channels
14.3.1 Physiological Roles
14.3.2 Subunit Diversity and Basic Structural Organization
14.3.3 Gating
14.3.4 Ion Permeability
14.3.5 Pharmacology
14.3.6 Regulation
14.3.7 Cell Biology (Biogenesis, Trafficking, Turnover)
14.4 Bestrophins
14.4.1 Physiological Roles
14.4.2 Subunit Diversity and Basic Structural Organization
14.4.3 Gating
14.4.4 Ion Permeability
14.4.5 Pharmacology
14.4.6 Regulation
14.4.7 Cell Biology
14.5 Channelopathies and Disease
14.5.1 TMEM16A and Cancer
14.5.2 TMEM16A Genetic Diseases
14.5.3 BEST1-Linked Diseases
14.6 Conclusions
Suggested Reading
Chapter 15 Acetylcholine Receptors
15.1 Introduction
15.2 Subunit Diversity and Cell Distribution
15.3 Physiological Roles
15.4 Structural Organization
15.4.1 Extracellular Domain (ECD) and Neurotransmitter Binding Sites
15.4.2 Transmembrane Domain (TMD) and Ion Permeation Pathway
15.4.3 Intracellular Domain (ICD)
15.4.4 Structural Changes for Activation
15.5 Molecular Function and Channel Gating
15.6 Pharmacology and Drug Modulation
15.6.1 Orthosteric Ligands
15.6.2 Allosteric Ligands
15.7 Channelopathies and Disease
15.7.1 Muscle and Ganglionic Diseases
15.7.2 Neurological and Neurodegenerative Disorders
15.7.3 Nicotine Dependence
15.7.4 Cancer and Inflammatory Disorders
15.8 Cell Biology and Regulation
15.9 Conclusions
Suggested Reading
Chapter 16 Ionotropic Glutamate Receptors
16.1 Introduction
16.2 Subunit Diversity; Genes/Paralogs/Orthologs/Subtypes; Alternative Splicing; Evolutionary Relationships
16.2.1 Splice Variation and RNA Editing
16.3 Structure/Organization
16.4 Physiological Roles; Expression Pattern
16.4.1 Basal Synaptic Transmission
16.4.2 Control of Vesicle Release
16.4.3 Synaptogenesis
16.4.4 Synaptic Plasticity: LTP and LTD
16.4.5 Short-Term Plasticity
16.4.6 Homeostasis
16.4.7 Expression Outside the Brain
16.5 Pore Properties (Selectivity, Permeation, Gate)
16.6 Pharmacology/Blockers
16.6.1 Competitive Antagonists
16.6.2 Noncompetitive Antagonists and Allosteric Modulators
16.6.3 Pore Blockers
16.6.4 Optical Methods
16.7 Gating Mechanisms, Agonist Selectivity, Subunit Contributions and Interactions
16.7.1 LBD Closure as the Driving Force of Channel Activation
16.7.2 Kinetics of Activation
16.7.3 Channel Gating
16.7.4 Intersubunit Interactions
16.7.5 Subunit Gating
16.8 Regulation (Second Messengers, Mechanisms, Related Physiology)
16.8.1 Phosphorylation
16.8.2 Other Posttranslational Modifications
16.8.3 Glutamate Receptor Action without Ion Flux
16.9 Cell Biology (Assembly, Trafficking, Associated Proteins)
16.9.1 Assembly
16.9.2 Transmembrane AMPA Receptor-Associated Proteins (TARPs)
16.9.3 Neto
16.9.4 Synaptic Trapping and Auxiliary Proteins
16.10 Channelopathies and Disease Mechanisms
Suggested Reading
Chapter 17 5-HT3 Receptors
17.1 Introduction
17.2 Subunit Diversity
17.3 Structure
17.3.1 The Extracellular Domain
17.3.2 The Transmembrane Domain
17.3.3 The Intracellular Domain
17.4 Physiological Roles and Expression
17.5 Biophysical Properties
17.5.1 Receptor Activation
17.5.2 Ions and Ionic Selectivity
17.5.3 Single-Channel Conductance
17.5.4 The Channel Gate
17.6 Pharmacology
17.6.1 5-HT3 Receptor Agonists
17.6.2 5-HT3 Receptor Antagonists
17.6.3 5-HT3 Receptor Modulators
17.7 Regulation
17.8 Cell Biology
17.9 Channelopathies and Therapeutic Potential
Suggested Reading
Chapter 18 GABAA Receptors
18.1 Introduction
18.2 Receptor Subunit Diversity and Structure
18.3 Receptor Trafficking and Clustering
18.4 Receptor Activation and GABA Binding Sites
18.5 Ion Channel Domain: Conductance and Ion Selection
18.6 Biophysical Properties of GABAARs: Influence of Subunit Composition
18.7 Modulation of GABAARs
18.7.1 ECD Interfacial Binding Sites: Agonists
18.7.2 Interfacial Binding Sites: Antagonists
18.7.3 Interfacial Binding Sites: Positive Allosteric Modulators
18.7.4 Interfacial Binding Sites: The Non-GABA Binding Interface
18.7.5 Transmembrane Domain Binding Sites: Intrasubunit and Interfacial
18.7.6 Transmembrane Binding Sites: The Ion Channel Pore
18.8 Conclusions
Suggested Reading
Chapter 19 Glycine Receptors
19.1 Introduction
19.2 Subunit Diversity and Basic Structural Organization
19.2.1 Structural Organization
19.3 Physiological Roles
19.4 Gating
19.5 Ion Permeability and Conductance
19.6 Pharmacology
19.7 Trafficking, Clustering and Regulation
19.8 Channelopathies and Disease
19.9 Conclusions
Suggested Reading
Chapter 20 Acid-Sensing Ion Channels
20.1 Introduction
20.2 Tissue Distribution
20.3 Function
20.4 Agonists, Modulators and Inhibitors
20.4.1 Agonists and Modulators
20.4.2 Inhibitors
20.5 Biophysical Properties
20.5.1 Structure and Gating
20.5.2 Desensitization
20.5.3 Ion Selectivity
20.6 Perspectives
Suggested Reading
Chapter 21 ENaC Channels
21.1 Introduction
21.2 Physiological Roles
21.2.1 ENaC in Epithelial Cells
21.2.2 ENaC in Non-Epithelial Tissues and Cells
21.3 Subunit Diversity and Basic Structural Organization
21.4 Gating
21.5 Ion Permeability
21.6 Pharmacology of ENaC
21.7 Regulation of ENaC
21.8 Cell Biology of ENaC: Biogenesis, Trafficking and Turnover
21.9 Channelopathies and Disease
21.10 Conclusion
Suggested Reading
Chapter 22 TRPC Channels
22.1 Introduction
22.2 Physiological Roles
22.3 Subunit Diversity and Basic Structural Organization
22.4 Gating
22.5 Ion Permeability
22.6 Pharmacology
22.7 Regulation
22.8 Channelopathies and Disease
22.9 Conclusions
Suggested Reading
Chapter 23 TRPM Channels
23.1 Introduction
23.2 TRPM
23.2.1 Molecular Structure
23.2.2 Cellular Function
23.3 TRPM
23.3.1 Molecular Structure
23.3.2 Cellular Function
23.4 TRPM
23.4.1 Molecular Structure
23.4.2 Cellular Function
23.5 TRPM
23.5.1 Molecular Structure
23.5.2 Cellular Function
23.6 TRPM
23.6.1 Molecular Structure
23.6.2 Cellular Functions
23.7 TRPM
23.7.1 Molecular Structure
23.7.2 Cellular Functions
23.8 TRPM
23.8.1 Molecular Structure
23.8.2 Cellular Function
23.9 TRPM
23.9.1 Molecular Structure
23.9.2 Cellular Function
Acknowledgments
Suggested Reading
Chapter 24 TRPV Channels
24.1 Introduction
24.2 Physiological Roles
24.2.1 TRPV
24.2.2 TRPV
24.2.3 TRPV
24.2.4 TRPV
24.2.5 TRPV5 and TRPV
24.3 Subunit Diversity and Basic Structural Organization
24.4 Gating by Temperature and Ligands
24.5 Ion Permeability and Pharmacology
24.6 Regulation
24.7 Biogenesis, Trafficking and Turnover
24.8 Channelopathies
24.9 Conclusions
Acknowledgments
Suggested Reading
Chapter 25 Store-Operated CRAC Channels
25.1 Introduction
25.2 Biophysical Properties of CRAC Channels
25.3 STIM1 Is the ER Ca2+ Sensor for CRAC Channel Activation
25.4 ORAI1 Is the Prototypic CRAC Channel Protein
25.5 Activation of STIM1: Oligomerization and Redistribution to ER–Plasma Membrane Junctions
25.6 STIM1 Binds Directly to ORAI
25.7 Pore Architecture and Gating
25.8 Tissue Distribution of STIM and ORAI Proteins
25.9 Physiological Functions of CRAC Channels
25.9.1 T Cells
25.9.2 Platelets
25.9.3 Skeletal Muscle
25.9.4 Nervous System
25.9.5 Cell Proliferation and Cancer
25.10 Conclusions
Acknowledgments
Suggested Reading
Chapter 26 Piezo Channels
26.1 Introduction
26.2 Physiological Roles
26.3 Subunit Diversity and Basic Structural Organization
26.4 Gating
26.5 Ion Permeability
26.6 Pharmacology
26.7 Regulation
26.8 Cell Biology
26.9 Channelopathies and Disease
26.10 Conclusions
Suggested Reading
Chapter 27 Ryanodine Receptors
27.1 Introduction
27.2 Physiological Role
27.3 Subunit Diversity and Basic Structural Organization
27.4 Gating and Ion Permeability
27.5 Pharmacology
27.6 Regulation
27.7 Cell Biology (Biogenesis, Trafficking, Turnover)
27.8 Channelopathies and Disease
27.9 Conclusions
Suggested Reading
Chapter 28 Proton Channels
28.1 Introduction
28.2 OTOP Channel Introduction
28.2.1 Physiological Roles of OTOP1 in Vestibular and Taste Systems
28.2.2 Gene Structure, Subunit Diversity, and Structure of OTOP Channels
28.2.3 Ion Selectivity, Pharmacology, and Gating of OTOP Channels
28.2.4 OTOP Channels Distribution and Related Diseases
28.3 Hv1 Channel Introduction
28.3.1 Physiological Roles of Hv1 Channels
28.3.2 Hv1 Structure
28.3.3 Hv1 Channel Gating
28.3.4 Ion Permeation and Selectivity in Hv
28.3.5 Hv1 Pharmacology
28.3.6 Hv1 Regulation
Note
Suggested Reading
Chapter 29 P2X Receptors
29.1 Introduction
29.2 Physiological Roles
29.3 Subunit Diversity and Basic Structural Organization
29.4 Gating
29.5 Ion Permeability
29.6 Pharmacology
29.7 Regulation
29.8 Cell Biology (Biogenesis, Trafficking, Turnover)
29.9 Channelopathies and Disease
29.10 Conclusion
Suggested Reading
Index
