9780878933211

Ion Channels of Excitable Membranes

by
  • ISBN13:

    9780878933211

  • ISBN10:

    0878933212

  • Edition: 3rd
  • Format: Hardcover
  • Copyright: 7/1/2001
  • Publisher: SINAUER ASSOC INC
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Summary

Univ. of Washington, Seattle. Text presenting new ideas in cell biology, focusing on ionic channels and excitable membranes. Significantly expanded from previous editions, featuring new material for students just entering the field. Not at expert level. Halftone illustrations, with a section of color computer-generated diagrams. Previous edition: c1992.

Table of Contents

Introduction
1(24)
Channels and ions are needed for excitation
2(3)
Channels get names
5(2)
Channels have families
7(1)
Ohm's law is central
7(3)
The membrane as a capacitor
10(3)
Equilibrium potentials and the Nernst equation
13(4)
Current-voltage relations of channels
17(4)
Ion selectivity
21(1)
Signaling requires only small ion fluxes
21(4)
PART I DESCRIPTION OF CHANNELS
Classical Biophysics of the Squid Giant Axon
25(36)
The action potential is a regenerative wave of Na+ permeability increase
26(7)
The voltage clamp measures current directly
33(2)
The ionic current of axons has two major components: I Na and I K
35(3)
Ionic conductances describe the permeability changes
38(4)
Two kinetic processes control g Na
42(3)
The Hodgkin-Huxley model describes permeability changes
45(7)
The Hodgkin-Huxley model predicts action potentials
52(2)
Do models have mechanistic implications?
54(2)
Voltage-dependent gates have gating charge and gating current
56(3)
The classical discoveries recapitualted
59(2)
The Superfamily of Voltage-Gated Channels
61(34)
Drugs and toxins help separate currents and identify channels
62(2)
Drugs and toxins act at receptors
64(5)
Gates open wide at the cytoplasmic end of the pore, and the pore narrows at the outside
69(2)
Early evidence for a pore came from biophysics
71(1)
There is a diversity of K channels
72(1)
Voltage-gated Na channels are less diverse
73(5)
Ion channels can be highly localized
78(3)
Voltage-gated channels form a gene superfamily
81(4)
The crystal structure shows a pore!
85(2)
Patch clamp reveals stochastic opening of single ion channels
87(5)
Recapitulation
92(3)
Voltage-Gated Calcium Channels
95(36)
Early work found Ca channels in every excitable cell
98(2)
Ca2+ ions can regulate contraction, secretion, and gating
100(8)
Ca2+ dependence imparts voltage dependence
108(2)
Multiple channel types: Dihydropyridine-sensitive channels
110(5)
Neurons have many HVA Ca-channel subtypes
115(2)
Voltage-gated Ca channels from a homologous gene family
117(2)
A note on Ca-channel nomenclature
119(1)
Permeation and ionic block require binding in the pore
120(4)
Do all Ca channels inactivate?
124(3)
Channel opening is voltage-dependent and delayed
127(1)
Overview of voltage-gated Ca channels
128(3)
Potassium Channels and Chloride Channels
131(38)
Fast delayed rectifiers keep short action potentials short
134(1)
Slow delayed rectifiers serve other roles
134(2)
Transient outward currents space repetitive responses
136(4)
Shaker opens the way for cloning and mutagenesis of K channels
140(3)
Ca2+-dependent K currents make long hyperpolarizing pauses
143(4)
Spontaneously active cells can serve as pacemakers
147(2)
Inward rectifiers permit long depolarizing responses
149(4)
What are Kir channels used for?
153(1)
The 4TM and 8TM K channels
154(1)
The bacterial KcsA channel is much like eukaryotic K channels
155(1)
An overview of K channels
156(2)
A hyperpolarization-activated cation current contributes to pacemaking
158(2)
Several strategies underlie slow rhythmicity
160(1)
Cl channels stabilize the membrane potential
160(2)
Cl channels have multiple functions
162(7)
Ligand-Gated Channels of Fast Chemical Synapses
169(32)
Ligand-gated receptors have several architectures
170(2)
Acetylcholine communicates the message at the neuromuscular junction
172(4)
Agonists can be applied to receptors in several ways
176(1)
The decay of the endplate current reflects channel gating kinetics
177(2)
Fluctuation analysis supported the Magleby-Stevens hypothesis
179(3)
The ACh receptor binds more than one ACh molecule
182(1)
Gaps in openings reveal slow agonist unbinding
183(1)
Agonist usually remains bound while the channel is open
184(1)
Ligand-gated receptors desensitize
184(1)
An allosteric kinetic model
185(2)
Recapitulation of nAChR channel gating
187(1)
The nicotinic ACh receptor is a cation-permeable channel with little selectivity
187(1)
Fast chemical synapses are diverse
188(3)
Fast inhibitory synapses use anion-permeable channels
191(4)
Excitatory amino acids open cation channels
195(4)
Recapitulation of fast chemical synaptic channels
199(2)
Modulation, Slow Synaptic Action, and Second Messengers
201(36)
cAMP is the classic second messenger
204(3)
cAMP-dependent phosphorylation augments ICa in the heart
207(4)
Rundown could be related to phosphorylation
211(1)
cAMP acts directly on some channels
211(1)
There are many G-protein-coupled second-messenger pathways
212(5)
ACh reveals a shortcut pathway
217(3)
Synaptic action is modulated
220(4)
G-protein-coupled receptors always have pleiotropic effects
224(2)
Encoding is modulated
226(2)
Pacemaking is modulated
228(4)
Slow versus fast synaptic action
232(2)
Second messengers are launched by other types of receptors
234(2)
First overview on second messengers and modulation
236(1)
Sensory Transduction and Excitable Cells
237(32)
Sensory receptors make an electrical signal
237(2)
Mechanotransduction is quick and direct
239(9)
Visual transduction is slow
248(2)
Vertebrate phototransduction uses cyclic GMP
250(7)
Phototransduction in flies uses a different signaling pathway
257(1)
Channels are complexed with other proteins
258(1)
Chemical senses use all imaginable mechanisms
259(2)
Pain sensation uses transduction channels
261(2)
What is an excitable cell?
263(6)
Calcium Dynamics, Epithelial Transport, and Intercellular Coupling
269(40)
Intracellular organelles have ion channels
269(5)
IP3-receptor channels respond to hormones
274(2)
Ca-release channels can be studied in lipid bilayers
276(2)
The ryanodine receptor of skeletal muscle has recruited a voltage sensor
278(5)
Voltage-gated Ca channels are the voltage sensor for ryanodine receptors
283(3)
IP3 is not the only Ca2+-mobilizing messenger
286(1)
Intracellular stores can gate plasma-membrane Ca channels
287(3)
The extended TRP family is diverse
290(1)
Mitochondria clear Ca2+ from the cytoplasm by a channel
291(1)
Protons have channels
292(1)
Transport epithelia are vectorially constructed
293(6)
Water moves through channels as well
299(1)
Cells are coupled by gap junctions
300(4)
All cells have other specialized intracellular channels
304(1)
Recapitulation of factors controlling gating
305(4)
PART II PRINCIPLES AND MECHANISMS OF FUNCTION
Elementary Properties of Ions in Solution
309(38)
Early electrochemistry
310(2)
Aqueous diffusion is just thermal agitation
312(3)
The Nernst-Planck equation describes electrodiffusion
315(4)
Uses of the Nernst-Planck equation
319(2)
Brownian dynamics describes electrodiffusion as stochastic motions of particles
321(1)
Electrodiffusion can also be described as hopping over barriers
322(4)
Ions interact with water
326(1)
The crystal radius is given by Pauling
326(2)
Ion hydration energies are large
328(3)
The ``hydration shell'' is dynamic
331(4)
``Hydrated radius'' is a fuzzy concept
335(3)
Activity coefficients reflect weak interactions of ions in solution
338(4)
Equilibrium ion selectivity can arise from electrostatic interactions
342(2)
Recapitulation of independence
344(3)
Elementary Properties of Pores
347(30)
Early pore theory
347(4)
Ohm's law sets limits on the channel conductance
351(1)
The diffusion equation also sets limits on the maximum current
352(2)
Summary of limits from macroscopic laws
354(1)
Dehydration rates can reduce mobility in narrow pores
355(1)
Single-file water movements can lower mobility
356(1)
Ion fluxes may saturate
357(1)
Long pores may have ion flux coupling
358(2)
Ions must overcome electrostatic barriers
360(2)
Ions could have to overcome mechanical barriers
362(1)
Gramicidin A is the best-studied model pore
363(6)
Electrostatic barriers are lowered in K channels
369(2)
A high turnover number is good evidence for a pore
371(3)
Some carriers have pore-like properties
374(1)
Recapitulation of pore theory
375(2)
Counting Channels and Measuring Fluctuations
377(28)
Neurotoxins count toxin receptors
378(1)
Gating current counts mobile charges within the membrane
379(4)
Digression on the amplitudes of current fluctuations
383(2)
Fluctuation amplitudes measure the number and size of elementary units
385(2)
A digression on microscopic kinetics
387(6)
The patch clamp measures single-channel currents directly
393(3)
Summary of single-channel conductance measurements
396(4)
Thoughts on the conductance of channels
400(2)
Channels are not crowded
402(3)
Structure of Channel Proteins
405(36)
The nicotinic ACh receptor is a pentameric glycoprotein
406(1)
Complete amino acid sequences were determined by cloning
407(4)
Ligand-gated receptors form a large homologous family
411(3)
Determining topology requires chemistry
414(5)
Electron microscopy shows a tall hourglass
419(2)
A partial crystal structure shows a pentameric ring
421(2)
Voltage-gated channels also became a gene superfamily
423(4)
Are K channels tetramers?
427(1)
Auxiliary subunits change channel function
428(5)
KcsA is a teepee
433(1)
Electron paramagnetic resonance probes structure
434(1)
Kv channels have a lot of mass hanging as a layer cake in the cytoplasm
435(2)
Excitatory GluRs combine parts of two bacterial proteins
437(3)
Is there a pattern?
440(1)
Selective Permeability: Independence
441(30)
Partitioning into the membrane can control permeation
442(3)
The Goldman-Hodgkin-Katz equations describe a partitioning-electrodiffusion model
445(4)
Uses of the Goldman-Hodgkin-Katz equations
449(1)
Derivation of the Goldman-Hodgkin-Katz equations
450(3)
A more generally applicable voltage equation
453(1)
Voltage-gated channels have high ion selectivity
454(6)
Other channels have low ion selectivity
460(2)
Ion channels act as molecular sieves
462(7)
Selectivity filters can be dynamic
469(1)
First recapitulation of selective permeability
469(2)
Selective Permeability: Saturation and Binding
471(32)
Ionic currents do not obey the predictions of independence
471(7)
Simple models for one-ion channels
478(5)
Na channel permeation can be described by state models
483(3)
Some channels must hold more than one ion at a time
486(3)
Single-file multi-ion models
489(5)
Multi-ion pores can select by binding
494(3)
Anion channels have complex transport properties
497(2)
Recapitulation of selective permeation
499(1)
What do permeation models mean?
500(3)
Classical Mechanisms of Block
503(36)
Affinity and time scale of the drug-receptor reaction
504(2)
Binding in the pore can make voltage-dependent block: Protons
506(5)
Some blocking ions must wait for gates to open: Internal TEA
511(5)
Local anesthetics give use-dependent block
516(4)
Local anesthetics alter gating kinetics
520(4)
Antiarrhythmic action
524(1)
State-dependent block of ligand-gated receptors
525(2)
Multi-ion channels may show multi-ion block
527(6)
STX and TTX are the most potent and selective blockers of Na channels
533(2)
Some scorpion toxins plug K channel pores
535(1)
Recapitulation of blocking mechanisms
536(3)
Structure-Function Studies of Permeation and Block
539(36)
Charges in the M2 segment help nAChR channels conduct
540(5)
What can a charged residue do?
545(3)
Channel blockers interact with M2 and M1 segments
548(3)
Cysteine substitution can test accessibility of residues
551(2)
The S5-S6 linker forms the outer funnel and pore in K channels
553(5)
The S5-S6 linker forms the outer funnel and pore in Na channels
558(3)
Divalent/monovalent selectivity depends on charge density and electrostatics
561(3)
The S6/M2 segment contributes to the inner pore
564(2)
Inward rectification is voltage-dependent block
566(6)
Functions are not independent
572(1)
Recapitulation of structure-function studies
573(2)
Gating Mechanisms: Kinetic Thinking
575(28)
First recapitulation of gating
575(2)
Proteins change conformation during activity
577(4)
Events in proteins occur across the frequency spectrum
581(2)
Topics in classical kinetics
583(6)
Additional kinetic measures are essential
589(5)
Most gating charge moves in significant steps
594(1)
A new round of kinetic models for Shaker K channel gating
594(3)
For BK channels we need three-dimensional kinetic models
597(2)
Nav and Cav channels require more complex models
599(1)
Channels can have several open states
600(2)
Conclusion of channel gating kinetics
602(1)
Gating: Voltage Sensing and Inactivation
603(32)
Simple equilibrium principles of voltage sensing and charge movement
603(2)
Early mutagenesis points to the S4 segment
605(3)
The S4 segment does carry much of the gating charge
608(4)
Several residues in S4 move fully across the membrane
612(3)
Movements around S4 are observed optically
615(2)
Recapitulation of voltage sensing
617(1)
What is a gate?
617(3)
Pronase clips inactivation gates
620(2)
Inactivation is coupled to activation
622(2)
Microscopic inactivation can be rapid and voltage-independent
624(4)
Fast inactivation gates are tethered plugs
628(3)
Fast inactivation of Na channels involves a cytoplasmic loop
631(1)
Slow inactivation is distinct from fast inactivation: A new gate?
632(2)
Recapitulation of inactivation gating
634(1)
Modification of Gating in Voltage-Sensitive Channels
635(28)
Many peptide toxins slow inactivation
636(5)
A group of lipid-soluble toxins changes many properties of Na channels
641(4)
Reactive reagents eliminate inactivation of Na channels
645(1)
External Ca2+ ions shift voltage-dependent gating
646(5)
Surface-potential calculations
651(6)
Much of the negative charge is on the channel
657(1)
Surface-potential theory has shortcomings
658(2)
Recapitulation of gating modifiers
660(1)
What are models for?
661(2)
Cell Biology and Channels
663(30)
Channel genes can be identified by classical genetics
664(3)
Expression of channels is dynamic during development
667(2)
Transcription of nAChR genes is regulated by activity, position, and cell type
669(4)
Channel mRNA can be alternatively spliced and edited
673(3)
Channel synthesis and assembly occurs on membranes
676(3)
Sequences on channel subunits are used for quality control
679(1)
Membrane proteins can be localized and immobilized
680(2)
nACh receptors become clustered and immobilized
682(5)
Multivalent PDZ proteins cluster channels at glutamatergic synapses
687(1)
Channels are sorted and move in vesicles
687(4)
Recapitulation
691(2)
Evolution and Origins
693(30)
Channels of lower animals resemble those of higher animals
699(2)
Channels are prevalent in eukaryotes and prokaryotes
701(4)
Channels mediate sensory-motor responses
705(4)
Channel evolution is slow
709(4)
Gene duplication and divergence create families of genes
713(3)
Proteins are mosaics
716(3)
Speculations on channel evolution
719(3)
Conclusion
722(1)
References 723(65)
Index 788

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