Ion channels of excitable membranes:
Saved in:
| Main Author: | |
|---|---|
| Format: | Book |
| Language: | English |
| Published: |
Sunderland, Massachusetts, US
Sinauer
2001
|
| Edition: | third edition |
| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Item Description: | Frühere Aufl. u.d.T.: Hille, Bertil: Ionic channels of excitable membranes Hier auch später erschienene, unveränderte Nachdrucke. |
| Physical Description: | xviii, 814 Seiten Illustrationen |
| ISBN: | 9780878933211 0878933212 |
Staff View
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| 245 | 1 | 0 | |a Ion channels of excitable membranes |c Bertil Hille |
| 250 | |a third edition | ||
| 264 | 1 | |a Sunderland, Massachusetts, US |b Sinauer |c 2001 | |
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| 500 | |a Hier auch später erschienene, unveränderte Nachdrucke. | ||
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Record in the Search Index
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|---|---|
| adam_text | Contents
CHAPTER 1 INTRODUCTION 1
Channels and ions are needed for excitation 2
Channels get names 5
Channels have families 7
Ohm s law is central 7
The membrane as a capacitor 10
Equilibrium potentials and the Nernst equation 13
Current voltage relations of channels 17
Ion selectivity 21
Signaling requires only small ion fluxes 21
PARTI
DESCRIPTION OF CHANNELS
CHAPTER 2 CLASSICAL BIOPHYSICS OF THE SQUID GIANT AXON 25
The action potential is a regenerative wave of Na+ permeability
increase 26
The voltage clamp measures current directly 33
The ionic current of axons has two major components: JNa
and /K 35
Ionic conductances describe the permeability changes 38
Two kinetic processes control gNa 42
viii Contents
The Hodgkin Huxley model describes permeability changes 45
The Hodgkin Huxley model predicts action potentials 52
Do models have mechanistic implications? 54
Voltage dependent gates have gating charge and gating
current 56
The classical discoveries recapitulated 59
CHAPTER 3 THE SUPERFAMILY OF VOLTAGE GATED CHANNELS 61
Drugs and toxins help separate currents and identify
channels 62
Drugs and toxins act at receptors 64
Gates open wide at the cytoplasmic end of the pore, and the pore
narrows at the outside 69
Early evidence for a pore came from biophysics 71
There is a diversity of K channels 72
Voltage gated Na channels are less diverse 73
Ion channels can be highly localized 78
Voltage gated channels form a gene superfamily 81
The crystal structure shows a pore! 85
Patch clamp reveals stochastic opening of single ion channels 87
Recapitulation 92
CHAPTER 4 VOLTAGE GATED CALCIUM CHANNELS 95
Early work found Ca channels in every excitable cell 98
Ca2+ ions can regulate contraction, secretion, and gating 100
Ca2+ dependence imparts voltage dependence 108
Multiple channel types: Dihydropyridine sensitive channels 110
Neurons have many HVA Ca channel subtypes 115
Voltage gated Ca channels form a homologous gene family 117
A note on Ca channel nomenclature 119
Permeation and ionic block require binding in the pore 120
Do all Ca channels inactivate? 124
Channel opening is voltage dependent and delayed 127
Overview of voltage gated Ca channels 128
CHAPTER 5 POTASSIUM CHANNELS AND CHLORIDE
CHANNELS 131
Fast delayed rectifiers keep short action potentials short 134
Slow delayed rectifiers serve other roles 134
Contents ix
Transient outward currents space repetitive responses 136
Shaker opens the way for cloning and mutagenesis of K
channels 140
Ca2+ dependent K currents make long hyperpolarizing
pauses 143
Spontaneously active cells can serve as pacemakers 147
Inward rectifiers permit long depolarizing responses 149
What are Kir channels used for? 153
The 4TM and 8TM K channels 154
The bacterial KcsA channel is much like eukaryotic
K channels 155
An overview of K channels 156
A hyperpolarization activated cation current contributes to
pacemaking 158
Several strategies underlie slow rhythmicity 160
Cl channels stabilize the membrane potential 160
Cl channels have multiple functions 162
CHAPTER 6 LIGAND GATED CHANNELS OF FAST CHEMICAL
SYNAPSES 169
Ligand gated receptors have several architectures 170
Acetylcholine communicates the message at the neuromuscular
junction 172
Agonists can be applied to receptors in several ways 176
The decay of the endplate current reflects channel gating
kinetics 177
Fluctuation analysis supported the Magleby Stevens
hypothesis 179
The ACh receptor binds more than one ACh molecule 182
Gaps in openings reveal slow agonist unbinding 183
Agonist usually remains bound while the channel is open 184
Ligand gated receptors desensitize 184
An allosteric kinetic model 185
Recapitulation of nAChR channel gating 187
The nicotinic ACh receptor is a cation permeable channel with
little selectivity 187
Fast chemical synapses are diverse 188
Fast inhibitory synapses use anion permeable channels 191
Excitatory amino acids open cation channels 195
Recapitulation of fast chemical synaptic channels 199
x Contents
CHAPTER 7 MODULATION, SLOW SYNAPTIC ACTION,
AND SECOND MESSENGERS 201
cAMP is the classic second messenger 204
cAMP dependent phosphorylation augments JCa in the heart 207
Rundown could be related to phosphorylation 211
cAMP acts directly on some channels 211
There are many G protein coupled second messenger
pathways 212
ACh reveals a shortcut pathway 217
Synaptic action is modulated 220
G protein coupled receptors always have pleiotropic effects 224
Encoding is modulated 226
Pacemaking is modulated 228
Slow versus fast synaptic action 232
Second messengers are launched by other types of receptors 234
First overview on second messengers and modulation 236
CHAPTER 8 SENSORY TRANSDUCTION
AND EXCITABLE CELLS 237
Sensory receptors make an electrical signal 237
Mechanotransduction is quick and direct 239
Visual transduction is slow 248
Vertebrate phototransduction uses cyclic GMP 250
Phototransduction in flies uses a different signaling
pathway 257
Channels are complexed with other proteins 258
Chemical senses use all imaginable mechanisms 259
Pain sensation uses transduction channels 261
What is an excitable cell? 263
CHAPTER 9 CALCIUM DYNAMICS, EPITHELIAL TRANSPORT, AND
INTERCELLULAR COUPLING 269
Intracellular organelles have ion channels 269
IP3 receptor channels respond to hormones 274
Ca release channels can be studied in lipid bilayers 276
The ryanodine receptor of skeletal muscle has recruited
a voltage sensor 278
Voltage gated Ca channels are the voltage sensor for
ryanodine receptors 283
Contents xi
IP3 is not the only Ca2+ mobilizing messenger 286
Intracellular stores can gate plasma membrane Ca channels 287
The extended TRP family is diverse 290
Mitochondria clear Ca2+ from the cytoplasm by a channel 291
Protons have channels 292
Transport epithelia are vectorially constructed 293
Water moves through channels as well 299
Cells are coupled by gap junctions 300
All cells have other specialized intracellular channels 304
Recapitulation of factors controlling gating 305
PART II
PRINCIPLES AND MECHANISMS OF FUNCTION
CHAPTER 10 ELEMENTARY PROPERTIES OF IONS IN SOLUTION 309
Early electrochemistry 310
Aqueous diffusion is just thermal agitation 312
The Nernst Planck equation describes electrodiffusion 315
Uses of the Nernst Planck equation 319
Brownian dynamics describes electrodiffusion as stochastic
motions of particles 321
Electrodiffusion can also be described as hopping
over barriers 322
Ions interact with water 326
The crystal radius is given by Pauling 326
Ion hydration energies are large 328
The hydration shell is dynamic 331
Hydrated radius is a fuzzy concept 335
Activity coefficients reflect weak interactions of ions
in solution 338
Equilibrium ion selectivity can arise from electrostatic
interactions 342
Recapitulation of independence 344
CHAPTER 11 ELEMENTARY PROPERTIES OF PORES 347
Early pore theory 347
Ohm s law sets limits on the channel conductance 351
xii Contents
The diffusion equation also sets limits on the maximum
current 352
Summary of limits from macroscopic laws 354
Dehydration rates can reduce mobility in narrow pores 355
Single file water movements can lower mobility 356
Ion fluxes may saturate 357
Long pores may have ion flux coupling 358
Ions must overcome electrostatic barriers 360
Ions could have to overcome mechanical barriers 362
Gramicidin A is the best studied model pore 363
Electrostatic barriers are lowered in K channels 369
A high turnover number is good evidence for a pore 371
Some carriers have pore like properties 374
Recapitulation of pore theory 375
CHAPTER 12 COUNTING CHANNELS AND MEASURING
FLUCTUATIONS 377
Neurotoxins count toxin receptors 378
Gating current counts mobile charges within the membrane 379
Digression on the amplitudes of current fluctuations 383
Fluctuation amplitudes measure the number and size
of elementary units 385
A digression on microscopic kinetics 387
The patch clamp measures single channel currents directly 393
Summary of single channel conductance measurements 396
Thoughts on the conductance of channels 400
Channels are not crowded 402
CHAPTER 13 STRUCTURE OF CHANNEL PROTEINS 405
The nicotinic ACh receptor is a pentameric glycoprotein 406
Complete amino acid sequences were determined by
cloning 407
Ligand gated receptors form a large homologous family 411
Determining topology requires chemistry 414
Electron microscopy shows a tall hourglass 419
A partial crystal structure shows a pentameric ring 421
Voltage gated channels also became a gene superfamily 423
Are K channels tetramers? 427
Auxiliary subunits change channel function 428
Contents xiii
KcsA is a teepee 433
Electron paramagnetic resonance probes structure 434
Kv channels have a lot of mass hanging as a
layer cake in the cytoplasm 435
Excitatory GluRs combine parts of two bacterial proteins 437
Is there a pattern? 440
CHAPTER 14 SELECTIVE PERMEABILITY: INDEPENDENCE 441
Partitioning into the membrane can control permeation 442
The Goldman Hodgkin Katz equations describe a
partitioning electrodiffusion model 445
Uses of the Goldman Hodgkin Katz equations 449
Derivation of the Goldman Hodgkin Katz equations 450
A more generally applicable voltage equation 453
Voltage gated channels have high ion selectivity 454
Other channels have low ion selectivity 460
Ion channels act as molecular sieves 462
Selectivity filters can be dynamic 469
First recapitulation of selective permeability 469
CHAPTER 15 SELECTIVE PERMEABILITY: SATURATION
AND BINDING 471
Ionic currents do not obey the predictions of independence 471
Simple models for one ion channels 478
Na channel permeation can be described by state models 483
Some channels must hold more than one ion at a time 486
Single file multi ion models 489
Multi ion pores can select by binding 494
Anion channels have complex transport properties 497
Recapitulation of selective permeation 499
What do permeation models mean? 500
CHAPTER 16 CLASSICAL MECHANISMS OF BLOCK 503
Affinity and time scale of the drug receptor reaction 504
Binding in the pore can make voltage dependent block:
Protons 506
Some blocking ions must wait for gates to open:
Internal TEA 511
xiv Contents
Local anesthetics give use dependent block 516
Local anesthetics alter gating kinetics 520
Antiarrhythmic action 524
State dependent block of ligand gated receptors 525
Multi ion channels may show multi ion block 527
STX and TTX are the most potent and selective
blockers of Na channels 533
Some scorpion toxins plug K channel pores 535
Recapitulation of blocking mechanisms 536
CHAPTER 17 STRUCTURE FUNCTION STUDIES OF
PERMEATION AND BLOCK 539
Charges in the M2 segment help nAChR channels conduct 540
What can a charged residue do? 545
Channel blockers interact with M2 and Ml segments 548
Cysteine substitution can test accessibility of residues 551
The S5 S6 linker forms the outer funnel and pore in
K channels 553
The S5 S6 linker forms the outer funnel and pore in
Na channels 558
Divalent/monovalent selectivity depends on charge density
and electrostatics 561
The S6/M2 segment contributes to the inner pore 564
Inward rectification is voltage dependent block 566
Functions are not independent 572
Recapitulation of structure function studies 573
CHAPTER 18 GATING MECHANISMS: KINETIC THINKING 575
First recapitulation of gating 575
Proteins change conformation during activity 577
Events in proteins occur across the frequency spectrum 581
Topics in classical kinetics 583
Additional kinetic measures are essential 589
Most gating charge moves in significant steps 594
A new round of kinetic models for Shaker K channel gating 594
For BK channels we need three dimensional kinetic models 597
Nav and Cav channels require more complex models 599
Channels can have several open states 600
Conclusion of channel gating kinetics 602
Contents xv
CHAPTER 19 GATING: VOLTAGE SENSING AND INACTIVATION 603
Simple equilibrium principles of voltage sensing
and charge movement 603
Early mutagenesis points to the S4 segment 605
The S4 segment does carry much of the gating charge 608
Several residues in S4 move fully across the membrane 612
Movements around S4 are observed optically 615
Recapitulation of voltage sensing 617
What is a gate? 617
Pronase clips inactivation gates 620
Inactivation is coupled to activation 622
Microscopic inactivation can be rapid and
voltage independent 624
Fast inactivation gates are tethered plugs 628
Fast inactivation of Na channels involves a cytoplasmic loop 631
Slow inactivation is distinct from fast inactivation:
A new gate? 632
Recapitulation of inactivation gating 634
CHAPTER 20 MODIFICATION OF GATING IN
VOLTAGE SENSITIVE CHANNELS 635
Many peptide toxins slow inactivation 636
A group of lipid soluble toxins changes many properties
of Na channels 641
Reactive reagents eliminate inactivation of Na channels 645
External Ca2+ ions shift voltage dependent gating 646
Surface potential calculations 651
Much of the negative charge is on the channel 657
Surface potential theory has shortcomings 658
Recapitulation of gating modifiers 660
What are models for? 661
CHAPTER 21 CELL BIOLOGY AND CHANNELS 663
Channel genes can be identified by classical genetics 664
Expression of channels is dynamic during development 667
Transcription of nAChR genes is regulated
by activity, position, and cell type 669
Channel mRNA can be alternatively spliced and edited 673
xvi Contents
Channel synthesis and assembly occurs on membranes 676
Sequences on channel subunits are used for quality control 679
Membrane proteins can be localized and immobilized 680
nACh receptors become clustered and immobilized 682
Multivalent PDZ proteins cluster channels
at glutamatergic synapses 687
Channels are sorted and move in vesicles 687
Recapitulation 691
CHAPTER 22 EVOLUTION AND ORIGINS 693
Channels of lower animals resemble those of higher animals 699
Channels are prevalent in eukaryotes and prokaryotes 701
Channels mediate sensory motor responses 705
Channel evolution is slow 709
Gene duplication and divergence create families of genes 713
Proteins are mosaics 716
Speculations on channel evolution 719
Conclusion 722
REFERENCES 723
INDEX 788
|
| any_adam_object | 1 |
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| dewey-full | 571.06/4 571.64 |
| dewey-hundreds | 500 - Natural sciences and mathematics |
| dewey-ones | 571 - Physiology & related subjects |
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| dewey-search | 571.06/4 571.64 |
| dewey-sort | 3571.06 14 |
| dewey-tens | 570 - Biology |
| discipline | Chemie / Pharmazie Physik Biologie Chemie |
| edition | third edition |
| format | Book |
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| id | DE-604.BV013639481 |
| illustrated | Illustrated |
| indexdate | 2024-07-09T18:49:26Z |
| institution | BVB |
| isbn | 9780878933211 0878933212 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-009319619 |
| oclc_num | 46858498 |
| open_access_boolean | |
| owner | DE-384 DE-355 DE-BY-UBR DE-20 DE-29 DE-91G DE-BY-TUM DE-19 DE-BY-UBM DE-703 DE-83 DE-11 DE-29T DE-188 |
| owner_facet | DE-384 DE-355 DE-BY-UBR DE-20 DE-29 DE-91G DE-BY-TUM DE-19 DE-BY-UBM DE-703 DE-83 DE-11 DE-29T DE-188 |
| physical | xviii, 814 Seiten Illustrationen |
| publishDate | 2001 |
| publishDateSearch | 2001 |
| publishDateSort | 2001 |
| publisher | Sinauer |
| record_format | marc |
| spelling | Hille, Bertil 1940- Verfasser (DE-588)139398627 aut Ion channels of excitable membranes Bertil Hille third edition Sunderland, Massachusetts, US Sinauer 2001 xviii, 814 Seiten Illustrationen txt rdacontent n rdamedia nc rdacarrier Frühere Aufl. u.d.T.: Hille, Bertil: Ionic channels of excitable membranes Hier auch später erschienene, unveränderte Nachdrucke. Cell Membranes cabt Physiology cabt Ion Channels cabt Ionenkanalen gtt Membranen gtt Cell Membrane physiology Cell membranes Ion Channels physiology Ion channels Muscle cells Neurons Biomembran (DE-588)4006884-5 gnd rswk-swf Signaltransduktion (DE-588)4318717-1 gnd rswk-swf Ionenkanal (DE-588)4138699-1 gnd rswk-swf Nervenzelle (DE-588)4041649-5 gnd rswk-swf Biomembran (DE-588)4006884-5 s Ionenkanal (DE-588)4138699-1 s DE-604 Nervenzelle (DE-588)4041649-5 s DE-188 Signaltransduktion (DE-588)4318717-1 s HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009319619&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Hille, Bertil 1940- Ion channels of excitable membranes Cell Membranes cabt Physiology cabt Ion Channels cabt Ionenkanalen gtt Membranen gtt Cell Membrane physiology Cell membranes Ion Channels physiology Ion channels Muscle cells Neurons Biomembran (DE-588)4006884-5 gnd Signaltransduktion (DE-588)4318717-1 gnd Ionenkanal (DE-588)4138699-1 gnd Nervenzelle (DE-588)4041649-5 gnd |
| subject_GND | (DE-588)4006884-5 (DE-588)4318717-1 (DE-588)4138699-1 (DE-588)4041649-5 |
| title | Ion channels of excitable membranes |
| title_auth | Ion channels of excitable membranes |
| title_exact_search | Ion channels of excitable membranes |
| title_full | Ion channels of excitable membranes Bertil Hille |
| title_fullStr | Ion channels of excitable membranes Bertil Hille |
| title_full_unstemmed | Ion channels of excitable membranes Bertil Hille |
| title_short | Ion channels of excitable membranes |
| title_sort | ion channels of excitable membranes |
| topic | Cell Membranes cabt Physiology cabt Ion Channels cabt Ionenkanalen gtt Membranen gtt Cell Membrane physiology Cell membranes Ion Channels physiology Ion channels Muscle cells Neurons Biomembran (DE-588)4006884-5 gnd Signaltransduktion (DE-588)4318717-1 gnd Ionenkanal (DE-588)4138699-1 gnd Nervenzelle (DE-588)4041649-5 gnd |
| topic_facet | Cell Membranes Physiology Ion Channels Ionenkanalen Membranen Cell Membrane physiology Cell membranes Ion Channels physiology Ion channels Muscle cells Neurons Biomembran Signaltransduktion Ionenkanal Nervenzelle |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009319619&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT hillebertil ionchannelsofexcitablemembranes |