Ion Channels in Biophysics and Physiology

✍ Scribed by Lei Zhou

• Publisher: Springer
• Year: 2022
• Tongue: English
• Leaves: 407
• Series: Advances in Experimental Medicine and Biology, 1349
• Edition: 1
• Category: Library

✦ Synopsis

This book gathers relatively recent and significant topics in the field of ion channel research. Ion channels form the molecular basis for membrane excitability in cells from the cardiovascular and nervous systems. In many non-excitable cells, ion channels contribute to diverse function including secretion of signaling compounds like hormones and insulin, cell volume regulation, intracellular signaling especially Ca2+ signaling, etc. Many human diseases have been attributed to abnormal channel functions and defective membrane expression of channel proteins. On the other hand, ion channels are excellent models for studying protein biophysics, especially the allosteric regulation of protein function by miscellaneous stimuli. Therefore, researches on ion channels carry significant meaning for the understanding of basic protein biophysics and diverse physiological functions and for developing novel and effective treatment for related human diseases. This book could provide graduates and scientists in both basic and clinical levels, a comprehensive understanding of cutting-edge advances and a useful and stimulating platform for tackling their own questions about ion channels.

✦ Table of Contents

Contents
Part I: Biophysical Mechanism
Chapter 1: Venom-Derived Peptides Inhibiting Voltage-Gated Sodium and Calcium Channels in Mammalian Sensory Neurons
1.1 Introduction
1.1.1 Sensory Neurons and Pain Signaling
1.1.2 Venom-Derived Peptides
1.2 Voltage-Gated Sodium Channels
1.3 Voltage-Gated Calcium Channels
References
Chapter 2: Advancing Ion Channel Research with Automated Patch Clamp (APC) Electrophysiology Platforms
2.1 Introduction
2.2 APC Platforms: Key Developments Over Two Decades
2.3 Early APC Adoption: Ion Channels in Drug Discovery
2.4 APC: Advancing Ion Channel Research
2.4.1 Control of Internal Cell Solution Dialysis or Exchange
2.4.2 Control of Experimental Temperature
2.4.3 Recording Site Fluid Applications: Microfluidics and Fixed-Well
2.4.4 Planar Patch Clamp Recording Plates
2.4.5 Multi-Hole Patch Clamp
2.4.6 Pressure Control
2.4.7 Optogenetics and Optical Stimulation
2.5 Concluding Remarks
References
Chapter 3: Ion Channels in Biophysics and Physiology: Methods and Challenges to Study Mechanosensitive Ion Channels
3.1 Mechanical Properties of Biological Materials
3.2 Detection of Mechanical Forces at the Cellular Level
3.3 Principles of Mechano-Electrical Transduction in Mechanosensitive Ion Channels
3.4 Families of Mechanosensitive Ion Channels
3.5 Experimental Methods to Stimulate Mechanosensitive Ion Channels
3.6 Computational Approaches to Study Gating Mechanisms in Mechanosensitive Ion Channels
References
Chapter 4: The Polysite Pharmacology of TREK K2P Channels
4.1 Introduction
4.2 The TREK Subfamily: Model Polymodal Ion Channels
4.3 The Polysite Pharmacology of TREK Channels
4.3.1 The Keystone Inhibitor Site: Block by Polynuclear Ruthenium Amines
4.3.2 The K2P Modulator Pocket: A Cryptic Small Molecule Binding Site for K2P Control
4.3.3 The Fenestration Site: A Binding Site for Activators and Inhibitors
4.3.4 The Modulatory Lipid Site: PIP2 and the C-Terminal Tail
4.4 Subtype Specific Modulators in the TREK Subfamily
4.5 Perspectives on K2P Channel Polysite Pharmacology
References
Chapter 5: Calcium Channel Splice Variants and Their Effects in Brain and Cardiovascular Function
5.1 Ion Channels in Biophysics and Physiology
5.1.1 Introduction to LTCC
5.1.2 Structure and Localization of LTCC
5.1.3 LTCC in the Cardiovascular System-Function
5.1.4 Channelopathies in the CVS-Cav1.2
5.1.4.1 Timothy Syndrome
5.1.4.2 Brugada Syndrome
5.1.5 Channelopathies in the CVS-Cav1.3
5.1.5.1 Cardiac Dysfunction/Arrhythmia
5.1.6 Regulation of Cav1.2
5.1.7 Conclusion
5.2 CaV2.1
5.2.1 History of CaV2.1 Channel
5.2.2 CaV2.1 Channel Diversity
5.2.3 Exon 31
5.2.4 Exon 37
5.2.5 Exon 43/44
5.2.6 Exon 47
5.2.7 Modulation of Calcium Channels
5.2.7.1 Voltage-Dependent Inactivation (VDI)
5.2.7.2 Ca2+-Dependent Inactivation (CDI)
5.2.7.3 Ca2+-Dependent Facilitation (CDF)
5.2.7.4 CaV2.1 Channelopathies
5.2.8 Episodic Ataxia Type 2 (EA2)
5.2.9 Familial Hemiplegic Migraine Type 1 (FHM1)
5.2.10 Spinocerebellar Ataxia Type 6 (SCA6)
5.2.11 Psychiatric Disorders
5.3 Conclusion
References
Chapter 6: Structure-Function of TMEM16 Ion Channels and Lipid Scramblases
6.1 Introduction
6.2 Molecular Identifications of TMEM16 Proteins
6.2.1 TMEM16A and TMEM16B Form the Canonical Ca2+-Activated Chloride Channels
6.2.2 TMEM16F Encodes a Dual Functional CaPLSase and Nonselective Ion Channel
6.3 Structure and Function of TMEM16 Proteins
6.3.1 Biophysical Properties of TMEM16 Ion Channels
6.3.2 Fluorescence Methods Enable Biophysical Characterization of TMEM16 CaPLSases
6.3.3 Overall Architecture of TMEM16 Proteins
6.3.4 Ca2+-Dependent Activation Mechanism
6.3.5 Voltage-Dependent Activation of TMEM16 Ion Channels
6.3.6 Ion Selectivity of the TMEM16A/B CaCCs
6.3.7 Ion Selectivity of the Dual-Functional TMEM16F
6.3.8 Phospholipid Permeation Through TMEM16 CaPLSases
6.3.8.1 Classical Credit Card´´ Model for Phospholipid Permeation 6.3.8.2 Membrane Bending/Distortion Is a Common Feature in TMEM16 Scramblases 6.3.8.3Lipidic Pore´´ Dual Permeation Model Derived from the Credit-Card´´ Model 6.3.8.4Ions-in-the-Pore and Lipids-Out-of-the-Groove´´ Dual Permeation Model
6.3.8.5 ``Alternating Pore-Cavity´´ Dual Permeation Model
6.3.9 TMEM16 CaPLSase Gating
6.4 Future Prospective
References
Chapter 7: Distribution and Assembly of TRP Ion Channels
7.1 Introduction
7.2 Distribution of TRP Channels and Its Implications for Health
7.2.1 Cellular Distribution of TRP Channels
7.2.2 TRP Channels Distribution in Healthy Tissues and Organs
7.2.2.1 Distribution of TRPCs in Mammals
TRPC1
TRPC2
TRPC3
TRPC4
TRPC5
TRPC6
TRPC7
7.2.2.2 Distribution of TRPMs in Mammals
TRPM1
TRPM2
TRPM3
TRPM4
TRPM5
TRPM6
TRPM7
TRPM8
7.2.2.3 Distribution of TRPVs in Mammals
TRPV1
TRPV2
TRPV3
TRPV4
TRPV5
TRPV6
7.2.2.4 Distribution of TRPA1 in Mammals
7.2.2.5 Distribution of TRPMLs in Mammals
7.2.2.6 Distribution of TRPPs in Mammals
7.2.3 TRP Channels in Abnormal Tissues and Organs
7.2.3.1 TRP Channels Distribution in Cancers
7.2.3.2 TRP Channels in Other Diseases
7.3 Assembly of TRP Channels
7.3.1 Intra-Subunit Interactions Affecting TRP Channel Assembly and Trafficking
7.3.2 Assembly of TRP Channels Within and Between Subfamilies
7.3.2.1 Assembly Within TRP Subfamilies
7.3.2.2 Assembly Between TRP Subfamilies
7.3.3 Assembly Between TRPP Channels and Receptor-like Polycystin-1 Family Proteins
7.3.4 Specificity of TRP Channel Subunits Co-Assembly
7.4 Discussion and Outlook
7.4.1 Relevance of TRP Channel Distribution to Their Function
7.4.2 Deciphering TRP Channel Assembly for a Better Understanding of Their Distribution and Functions
7.4.3 Summary
References
Chapter 8: Regulation of Ion Channel Function by Gas Molecules
8.1 Ion Channels in General
8.2 Chemical Physics of Gasotransmitters in General
8.3 Ion Channel Modification Via NO-Mediated S-Nitrosylation
8.3.1 NMDA Receptors
8.3.2 Voltage-Gated Na+ Channels
8.3.3 Acid Sensing Ion Channels (ASICs)
8.3.4 Cyclic-Nucleotide-Gated Ion Channels
8.3.5 Transient Receptor Potential Channels
8.3.6 Voltage-Gated K+ Channels
8.3.7 ATP-Sensitive Potassium Channels
8.3.8 Large-Conductance Ca2+-Activated K+ Channels
8.3.9 Voltage-Gated Ca2+ Channels
8.3.10 Ryanodine Receptors
8.4 Ion Channel Modification Via H2S and S-Sulfhydration
8.4.1 ATP-Sensitive Potassium Channels
8.4.2 Transient Receptor Potential Channels
8.4.3 L-Type Calcium Channels
8.5 Singlet Oxygen
8.6 Carbon Monoxide (CO) as a Gasotransmitter and Crosstalk Among Different Regulatory Pathways
References
Chapter 9: DEG/ENaC Ion Channels in the Function of the Nervous System: From Worm to Man
9.1 Introduction
9.2 DEG/ENaC Channels Structure
9.3 Modulation of DEG/ENaCs by Homologous and Accessory Subunits
9.4 Neuronal DEG/ENaC Channels in Mechanosensation
9.5 Neuronal DEG/ENaC Channels in Other Sensory Modalities
9.6 DEG/ENaC Channels in Neurotoxicity and Axonal Degeneration
9.7 C. elegans DEG/ENaC Channel UNC-8 is Involved in Synaptic Remodeling
9.8 DEG/ENaC Channels in Synaptic Transmission
9.9 Expression and Function of DEG/ENaC Channels in Glia
References
Part II: Physiological Function
Chapter 10: Glial Chloride Channels in the Function of the Nervous System Across Species
10.1 ClC-2
10.1.1 Structure and Function
10.1.2 ClC-2 in the Vertebrate Brain
10.1.3 Insights into the Function of Glial ClC Channels from Studies in Invertebrates
10.2 Acid and Swelling-Activated Cl- Channels (LRRC8 or SWELL1)
10.3 Acid-Sensitive Outwardly Rectifying (ASOR) Anion Channels
10.4 Maxi Chloride Channels
10.5 Pannexins as Cl- Channels
10.5.1 Structure and Function
10.5.2 Pannexins in the Nervous System of Vertebrates
10.5.3 Invertebrate Innexins
10.6 Bestrophins
10.6.1 Structure and Function
10.6.2 Bestrophins in the Mammalian Nervous System
10.6.3 Bestrophins in Invertebrates
References
Chapter 11: Physiological and Pathological Relevance of Selective and Nonselective Ca2+ Channels in Skeletal and Cardiac Muscle
11.1 Introduction
11.2 L-Type Ca2+ Channels and Ryanodine Receptors form the Core Functional Unit of Excitation-Contraction Coupling
11.3 Ca2+ Permeation Through Voltage-Insensitive Channels Is Altered in Striated Muscle Under Pathological States
References
Chapter 12: TRPV1 in Pain and Itch
12.1 Introduction
12.2 TRPV1 Biology in Pain and Itch
12.2.1 The Basics of Pain and Itch
12.2.2 TRPV1 and TRPV1+ Sensory Neurons
12.2.3 TRPV1 in Pain Sensation
12.2.3.1 Pain Classification
12.2.3.2 TRPV1 Serves as the Sensor for Pain Sensation
12.2.3.3 TRPV1+ Sensory Neuron in Pain Sensation
12.2.3.4 TRPV1-TRPA1 Complex in Pain Sensation
12.2.4 TRPV1 in Itch Sensation
12.2.4.1 Itch Is a Distinct Neural Process from Pain
12.2.4.2 TRPV1+ Sensory Neuron in Itch Sensation
12.2.4.3 Role of TRPV1 Ion Channel for Itch Signaling
12.3 TRPV1 Activity Modulation in Pain and Itch
12.3.1 TRPV1 Upregulation in the Context of Pain
12.3.2 TRPV1 Upregulation in the Context of Chronic Itch
12.3.3 TRPV1 Structure Modulation
12.3.4 TRPV1 Phosphorylation
12.3.4.1 PKC Pathway
12.3.4.2 PKA Pathway
12.3.4.3 CaMKII-Dependent Phosphorylation
12.3.5 Other Modulators
12.3.5.1 Protons
12.3.5.2 Pirt
12.3.5.3 GABA-Autocrine Feedback
12.3.6 Pain-to-Itch Switch
12.4 TRPV1+ Neurons as the Center of Neuroimmune Interactions
12.4.1 Mast Cells: A Classic Neuroimmune Paradigm
12.4.2 Beyond Mast Cells: Other Immune Cells Regulated by Nociceptors
12.5 Therapeutic Strategy and Perspectives
12.5.1 Agonist
12.5.2 Antagonist
12.5.3 TRPV1 Activity-Dependent Silencing by QX-314
12.6 Summary
References
Chapter 13: Lysosomal TRPML1 Channel: Implications in Cardiovascular and Kidney Diseases
13.1 Introduction
13.2 Characteristics of Lysosomal TRPML1 Channels
13.2.1 Subcellular Localization of Mammalian TRPML1 Channels
13.2.2 Biophysical Properties of TRPML1 Channels
13.3 Agonists and Blockers of TRPML1 Channel
13.3.1 NAADP
13.3.2 Phosphoinositides
13.3.3 Synthetic Agonists and Blockers
13.4 Associated Proteins of TRPML1 Channel
13.4.1 ALG-2
13.4.2 Hsc70
13.4.3 LAPTM
13.5 Regulatory Mechanisms of TRPML1 Channel Activity
13.5.1 Cathepsin B
13.5.2 TOR-TFEB Signaling Pathway
13.5.3 Phosphorylation
13.5.4 Regulation of TRPML1 Channel Activity by Sphingolipids
13.5.5 Redox Regulation of TRPML1 Channel Activity
13.6 Functions of TRPML1 Channels in Health and Diseases
13.6.1 Lysosomal pH Control
13.6.2 Fusion and Fission of Cell Membrane
13.6.3 Autophagy
13.6.4 Lysosomal Exocytosis
13.6.5 Mitochondrial Function
13.6.6 Triggering of Large Ca2+ Release from Sarcoplasmic Reticulum
13.6.7 Podocyte Differentiation and Podocytopathy
13.6.8 Exosome Release and Arterial Medial Calcification
13.6.9 Lysosome-Mediated Autophagic Flux and Atherogenesis
13.7 Concluding Remarks
References
Chapter 14: Store-Operated Calcium Entry in the Cardiovascular System
14.1 Introduction
14.2 Cardiac Excitation-Contraction Coupling
14.3 Expression of SOCE Components in the Heart
14.3.1 STIM
14.3.2 ORAI
14.3.3 TRPC
14.4 SOCE During Cardiac Development
14.5 SOCE in the Vascular System
14.5.1 SOCE in Vascular Smooth Muscle Cells
14.5.2 SOCE in Endothelial Cells
14.5.3 SOCE and Vascular Diseases
14.5.3.1 Thrombosis
14.5.3.2 Restenosis
14.5.3.3 Atherosclerosis
14.5.3.4 Systemic Arterial Hypertension
14.5.3.5 Pulmonary Arterial Hypertension
14.6 SOCE and Cardiac Diseases (see Table 14.1)
14.6.1 Cardiac Hypertrophy and Heart Failure
14.6.2 Arrhythmias
References
Chapter 15: Physiological Functions, Biophysical Properties, and Regulation of KCNQ1 (KV7.1) Potassium Channels
15.1 Introduction
15.2 Physiological Roles for KV7.1 and IKs Channels
15.3 KV7.1 and KCNQ1/KCNEx Channel Biophysics
15.4 KV7.1 Channel Structure
15.5 KCNQ1 Channel Pharmacology
15.6 KCNQ1 Channel Regulation
15.7 KCNQ1 and Disease
15.7.1 Cardiac Arrhythmias
15.7.2 Diabetes and Cancer
References
16: The Role of Thermosensitive Ion Channels in Mammalian Thermoregulation
16.1 Introduction
16.2 The Organization of the Thermoregulatory Circuits
16.2.1 Thermal Afferent Pathways
16.2.2 Efferent Pathways Controlling Thermoeffectors
16.3 Thermosensitive Ion Channels and Their Functions in Thermoregulation
16.3.1 Thermosensitive Properties of the Ion Channels
16.3.1.1 TRP Channels
TRPM8
TRPA1
TRPC5
TRPV1
TRPV2
TRPV3
TRPV4
TRPM2
TRPM3
16.3.1.2 TREK Channels
16.3.1.3 ANO1 (TMEM16A)
16.3.1.4 STIM1-ORAI1 Channel Complex
16.4 Summary
References
Chapter 17: Mechanotransduction Ion Channels in Hearing and Touch
17.1 Introduction
17.2 Mechanosensitive Ion Channels in Touch Sensation
17.2.1 NOMPC in Gentle Touch Sensation
17.2.2 Mechanogating Mechanism of NOMPC
17.2.3 Drosophila Brv1 in Light Touch Sensation
17.3 Mammalian TMCs in Hearing
17.3.1 Molecular Components of MET Channels in Hair Cells
17.3.2 Evidence Supporting TMC as Pore-Forming Subunit of the MET Channel
17.3.3 Recent Evidence for TMC as a Mechanosensitive Channel
17.4 Conclusions and Perspectives
References
Chapter 18: The Functional Properties, Physiological Roles, Channelopathy and Pharmacological Characteristics of the Slack (KC...
18.1 The Slack Channel (Slo2.2, KCNT1, KCa4.1)
18.2 Structural and Functional Domains of Slack Channels
18.3 The Phosphorylation Modulation on the Gating and Membrane Expression of the Slack Channel
18.4 The Expression Patterns and Physiological Function of the Slack Channel
18.5 The Role of the Slack Channel in Pain and Itch Sensing
18.6 The Possible Role of Slack Channel in FMRP Syndrome
18.7 The Basic Role of the Potassium Channel in Controlling Neuron Excitability
18.8 The Potential Roles of Slack Channel in Auditory Signal Transduction
18.9 The Role of KCNT1 Channel Mutations in Epilepsy
18.10 The Pharmacological Properties of the KCNT1 Channel and Potential Drugs for the Treatment of Epilepsy That Are Associate...
18.11 Conclusive Remarks
References
Chapter 19: Ion Channels in Anesthesia
19.1 GABAA Receptor
19.2 Cholinergic Receptor
19.3 Glutamate Receptor
19.4 Two-Pore-Domain Background K+ Channel
19.5 Conclusion
References