Biological Membrane Ion Channels (eBook)

Preface 6
Contents 9
List of Contributors 11
Part I Introduction 15
1 Ion Channels, from Fantasy to Fact in Fifty Years1 16
1.1 Introduction 16
1.2 Classical Biophysics 17
1.3 Pharmacology and Single Channels 20
1.4 Patch Clamp, Sequencing, and Mutagenesis 22
1.5 Structure 24
1.6 Spectroscopy 27
1.7 Theory 29
1.8 WhatÌs Next? 32
Acknowledgments 33
References 33
Part II Specific Channel Types 43
2 Gramicidin Channels: Versatile Tools 44
2.1 Overview 44
2.2 Introduction 44
2.3 Structure 45
2.4 Channel Function 60
2.5 Molecular Dynamics Analysis of Ion Permeation 75
2.6 Conclusion 78
Acknowledgments 79
References 79
3 Voltage-Gated Ion Channels 92
3.1 Introduction 92
3.2 Voltage-Dependent Ion Channels Are Membrane Proteins 93
3.3 The Parts of the Voltage-Dependent Channel 94
3.4 Gating Charge and the Voltage Sensor 97
3.5 Structural Basis of the Gating Charges 106
3.6 Structural Basis of the Voltage Sensor 107
3.7 Coupling of the Sensor to the Gate 120
3.8 Concluding Remarks 120
3.9 Outlook 122
Acknowledgments 123
References 123
4 Voltage-Gated Potassium Channels 130
Part I. Overview 130
4.1 Basics of K+ Channel Structure 131
4.2 Functional Classification 134
4.3 Summary 137
Part II. K+ Channel Operation 4.4 Control of Single- Channel Conductance 138
4.5 Activation Gates 140
4.6 Functions of the Outer Vestibule 144
4.7 Functions of the N-Terminal Domain 148
4.8 Modulation at the C-Terminal Domain 150
4.9 The MinK/MiRP Family of Accessory Subunits 152
Part III. Specific Properties of Voltage-Gated Channels 4.10 Diversity of Function 154
4.11 Kv1 Channels 155
4.12 Kv2 Channels 158
4.13 Kv3 Channels 162
4.14 Kv4 Channels 164
Acknowledgments 168
References 168
5 BKCa- Channel Structure and Function 182
5.1 Introduction 182
5.2 BKCa- Channel Topology 182
5.3 The Origin of the BKCa ChannelÌs Large Conductance 184
5.4 BKCa- Channel Gating, Studies Before Cloning 187
5.5 BKCa- Channel Gating, Macroscopic Current Properties 188
5.6 A Simple Model of BKCa- Channel Gating 190
5.7 Interpreting Mutations 200
5.8 A Better Model of Voltage-Dependent Gating 200
5.9 Combining HCA and MWC 204
5.10 The BKCa Channel Has Low- Affinity Ca2+ Binding Sites 208
5.11 The BKCa Channel Has Two Types of High- Affinity Ca2+- Binding Sites 210
5.12 Is the BKCa Channel Like the MthK Channel? 213
5.13 The Discovery of 216
1 216
5.14 Four 217
Subunits Have Now Been Identified 217
5.15 Conclusions 221
References 221
6 Voltage-Gated Sodium Channels 230
6.1 Introduction 230
6.2 The Sodium Channel as a Protein 231
6.3 The Pore 232
6.4 Gating 237
6.5 Hereditary Sodium Channel Diseases 244
Acknowledgments 245
References 245
7 Calcium Channels 251
7.1 Introduction 251
7.2 Types of Ca2+ Channels 252
7.3 Roles of Ca2+ Channels 260
7.4 Ion Selectivity and Permeation 264
7.5 Channel Structure 268
7.6 Theoretical Models of Permeation and Selectivity 272
7.7 Channel Gating 277
7.8 Inactivation of HVA Channels 280
7.9 Regulation of Channel Function 284
7.10 Conclusions and Outlook 289
References 291
8 Chloride Transporting CLC Proteins1 310
8.1 Introduction 310
8.2 Overview Over the Family of CLC Proteins 312
8.3 Architecture of CLC Proteins 318
8.4 Gating of CLC-0 and Mammalian CLC Channels 321
8.5 Permeation of CLC-0 and Mammalian CLC Channels 324
8.6 The X-ray Structure and Its Functional Implication: A Pivot Glutamate Controls the Protopore Gate 324
8.7 The Function as a Cl-/ H+ Antiporter 326
8.8 Pharmacology 328
8.9 CBS Domains 330
8.10 Conclusion 331
Acknowledgment 331
References 331
9 Ligand-Gated Ion Channels: Permeation and Activation1 343
9.1 Introduction 343
9.2 Physicochemical Structure 347
9.3 Ion Conductances, Permeation and Selectivity 353
9.4 Ion Channel Gating 362
9.5 Conclusions and Some Questions Still Pending 369
Acknowledgments 369
References 370
10 Mechanosensitive Channels 376
10.1 Introduction 376
10.2 Evolutionary Origins of MS Channels 377
10.3 Bilayer and Tethered Model of MS Channel Gating by Mechanical Force 378
10.4 MS Channels of Bacteria and Archaea 383
10.5 MS Channels of Eukaryotes 386
10.6 The Role of MS Channels in Cell Physiology and Pathology of Disease 392
10.7 Conclusion 394
Acknowledgments 395
References 395
11 TRP Channels 406
11.1 Introduction 406
11.2 TRP Channel History 406
11.3 Classification 407
11.4 Structural Aspects 408
11.5 Activation Mechanisms 414
11.6 Concluding Remarks 421
Acknowledgments 422
References 422
12 Ion Channels in Epithelial Cells 431
12.1 Ion Channels and Epithelial Function 431
12.2 Structural and Evolution of Epithelial Channels 435
12.3 Functional Specializations of Epithelial Ion Channels 439
12.4 Regulation of Epithelial Ion Channels 443
12.5 Summary 447
References 447
Part III Theoretical Approaches 452
13 PoissonÒNernstÒPlanck Theory of Ion Permeation Through Biological Channels 453
13.1 Introduction 453
13.2 Basic (Primitive) PNP Theory (and Its Limitations) 455
13.3 Numerical Algorithms for Solving the 3D PNP Equations 463
13.4 Application of Primitive PNP to Gramicidin A in Charged/ Dipolar Lipid Bilayers 465
13.5 Incorporating Ion (De)Hydration Energy Effects into PNP: DSEPNP 468
13.6 Incorporating Effects of Channel Protein Fluctuation in PNP: PMFPNP 472
13.7 Conclusions and Outlook 481
Acknowledgments 483
References 483
15 Brownian Dynamics: Simulation for Ion Channel Permeation1 510
15.1 Introduction 510
15.2 Stochastic Dynamics Simulations 512
15.3 Application of Brownian Dynamics in Ion Channels 516
15.4 Mathematical Formulation of Brownian Dynamics Algorithm 523
15.5 Probabilistic Characterization of Channel Conductance 529
15.6 Brownian Dynamics Simulation 535
15.7 Adaptive Controlled Brownian Dynamics Simulation 537
15.8 Concluding Remarks 539
References 542
16 Molecular Dynamics Simulation Approaches to K Channels 547
16.1 Introduction: Potassium Channels 547
16.2 Homology Modeling 548
16.3 MD Simulations of Ion Channels 550
16.4 Essential Dynamics of Ion Channels 551
16.5 What Can Simulations Tell Us? 554
16.6 Future Perspectives 562
Acknowledgments 563
References 563
Part IV Emerging Technologies 570
17 Patch-Clamp Technologies for Ion Channel Research 571
17.1 Introduction 571
17.2 Recordings of Ion Channel Activity 573
17.3 Planar Patch-Clamp Technologies 579
17.4 Simultaneous Electrical and Fluorescence Measurements 586
17.5 The Grand Challenge: Single-Charge Detection 586
17.6 Future Prospects 589
Acknowledgment 590
References 590
18 Gated Ion Channel-Based Biosensor Device 594
18.1 Introduction 594
18.2 Membrane-Based Biosensors 594
18.3 The Ion Channel Switch ICSTM Biosensor 595
18.4 Fabrication of a Membrane-Based Biosensor 596
18.5 Mechanism of Operation 604
18.6 Biosensor Characterization 611
18.7 Further Developments 614
Acknowledgments 615
References 615
19 Signal Processing Based on Hidden Markov Models for Extracting Small Channel Currents 621
19.1 Introduction 621
19.2 General Description of the HMM Method 622
19.3 HMM Formulation and Estimation Problems 627
19.4 Problem 1: Bayesian State Estimation of HMM 633
19.5 Problem 2: HMM Maximum Likelihood Parameter Estimation 637
19.6 Discussion 641
Reference 645
Index 649