Dedication

In Memoriam

Contributors

Foreword to the First Edition

Foreword to the Second Edition

Foreword to the Third Edition

Foreword to the Fourth Edition

Preface

Section I Biophysical Chemistry, Metabolism, Second Messengers, and Ultrastructure

Chapter 1. Biophysical Chemistry of Physiological Solutions

I Summary

II Introduction

III Structure and Properties of Water

IV Interactions Between Water and Ions

V Protons in Solution

VI Interactions Between Ions

VII Solute Transport: Basic Definitions

VIII Measurement of Electrolytes and Membrane Potential

Appendix: Thermodynamics of Membrane Transport

AII Nernst Equilibrium

BIBLIOGRAPHY

Chapter 2. Physiological Structure and Function of Proteins

I Summary

II Molecular Structure of Proteins

III Techniques for the Determination of the Structures of Proteins

IV Bulk Properties of Proteins: Proteins as Polyelectrolytes

V Relationship of Protein Structure to Function

BIBLIOGRAPHY

Chapter 3. Cell Membranes

I Summary

II The Bimolecular Lipid Membrane

III Membrane Lipids and Proteins

IV The Fluid Mosaic Model of Cell Membranes

BIBLIOGRAPHY

Chapter 4. Ionophores in Planar Lipid Bilayers

I Summary

II Ionophores

III Planar Lipid Bilayers

IV Ion Channel Properties in Planar Lipid Bilayers

V Gramicidin

BIBLIOGRAPHY

Chapter 5. Cell Structure

I Introduction

II Techniques

III Cell Theory

IV The Plasma Membrane as the Basis of Cellularity

V Nucleus

VI Endoplasmic Reticulum

VII Golgi Apparatus

VIII Lysosomes

IX Mitochondria

X Cytoskeleton

XI Cell Junctions

XII Special Tissues, Specialized Ultrastructure

Acknowledgments

BIBLIOGRAPHY

Chapter 6. Signal Transduction and Second Messengers

I What is Signal Transduction?

II General Principles

III General Types of Signal Transduction Cascades and their Components

IV Phosphorylation by Kinases and Other Post-translational Modifications

V Intracellular Signal Transduction Pathways

VI Conclusions

BIBLIOGRAPHY

Chapter 7. Calcium as an Intracellular Second Messenger

I Introduction

II Determination of Ca2+ Involvement in Physiological Processes

III Ca2+ as an Intracellular Signal

IV Creation of the Ca2+ Signal

V Mediation of the Ca2+ Signal

VI Ca2+-Calmodulin Dependent Protein Kinase II

VII Annexins: Calcium-Dependent Phospholipid-Binding Proteins

VIII Protein Kinase C

IX Current Perspectives

X Summary

BIBLIOGRAPHY

Section II Membrane Potential, Transport Physiology, Pumps, and Exchangers

Chapter 8. Diffusion and Permeability

I Summary

II Introduction

III Fick’s Law of Diffusion

IV Diffusion Coefficient

V Diffusion Across a Membrane with Partitioning

VI Permeability Coefficient

VII Electrodiffusion

VIII Special Transport Processes

IX Ussing Flux Ratio Equation

BIBLIOGRAPHY

Chapter 9. Origin of Resting Membrane Potentials

I Summary

II Introduction

III Passive Electrical Properties

IV Maintenance of Ion Distributions

V Equilibrium Potentials

VI Electrochemical Driving Forces and Membrane Ionic Currents

VII Determination of Resting Potential and Net Diffusion Potential (Ediff)

VIII Electrogenic Sodium Pump Potentials

Appendix

AII Derivation of Nernst Equation

AIII Half-Cell Potentials

AIV Constant-Field Equation Details

AV Derivation of Chord Conductance Equation

AVI Circuit Analysis Applicable to Cell Membrane

BIBLIOGRAPHY

Chapter 10. Gibbs–Donnan Equilibrium Potentials

I Summary

II Introduction

III Mechanism for Development of the Gibbs–Donnan Potential

IV Gibbs–Donnan Equilibrium

V Quantitation of the Gibbs–Donnan Potential

VI Osmotic Considerations

BIBLIOGRAPHY

Chapter 11. Mechanisms of Carrier-Mediated Transport

I Summary

II Introduction

III Electrochemical Potential

IV Carrier-Mediated Transport Mechanisms

BIBLIOGRAPHY

Chapter 12. Active Ion Transport by ATP-Driven Ion Pumps

I Summary

II Introduction

III Classes of ATP-driven Ion Pumps

IV The Albers–Post Mechanism of Ion Transport by P-type Ion Pumps

V Structures of P-type Ion Pumps

VI Beta Subunits

VII Isoforms of Pump Subunits and Subfamilies of P-type Pumps

VIII FXYD Proteins

IX Regulation of P-type ATPase Activity

X Pharmacological Inhibitors of P-type ATPases

BIBLIOGRAPHY

Chapter 13. Ca-ATPases

I Introduction

II Sarcoplasmic Reticular (SR) Ca2+-ATPase

III Other ATPases

IV Overview

Acknowledgments

BIBLIOGRAPHY

Chapter 14. Na-Ca Exchange Currents

I Summary

II Introduction

III Energetics of Na+-Ca2+ Exchange

IV Methods and Problems Associated with the Measurement of Na+-Ca2+ Exchange Current

V Isolation of Na+-Ca2+ Exchange Current

VI Ionic Dependencies of Na+-Ca2+ Exchange Current

VII Regulation of Na+-Ca2+ Exchange Current

VIII Structure of NCX and its Relationship to Function

IX The Phylogeny of the Na+-Ca2+ Exchanger

X Isoforms of the Na+-Ca2+ Exchanger

XI Current–Voltage Relationships and Voltage Dependence of Na+-Ca2+ Exchange Current

XII Mechanism of Na+-Ca2+ Exchange

XIII Na+-Ca2+ Exchange Currents During the Cardiac Action Potential

XIV Na+-Ca2+ Exchange Currents and Excitation–Contraction Coupling

BIBLIOGRAPHY

Chapter 15. Intracellular Chloride Regulation

I Introduction

II Origin of the Passive Cl− Distribution Assumption

III Passive and Non-passive Cl− Distribution Across the Plasma Membrane

IV Active Transport Mechanisms for Cl−

V Electroneutral Na+-K+-Cl− Cotransporters

VI Electroneutral K+-Cl− Cotransporters

VII Electroneutral Na+-Cl− Cotransporter

Acknowledgments

BIBLIOGRAPHY

Chapter 16. Osmosis and Regulation of Cell Volume

I Summary

II Introduction

III Water Movement Across Model Membranes

IV Mechanisms of Osmosis

V Water Movement Across Cell Membranes

VI Regulation of Cell Volume under Isosmotic Conditions

VII Regulation of Cell Volume under Anisosmotic Conditions

Acknowledgments

BIBLIOGRAPHY

Chapter 17. Intracellular pH Regulation

I Summary

II Introduction

III pH and Buffering Power

IV Intracellular pH

V Organellar pH

VI Maintenance of a Steady-State pHi

VII Active Membrane Transport of Acids and Bases

VIII Cellular Functions Affected by Intracellular pH

BIBLIOGRAPHY

Section III Membrane Excitability and Ion Channels

Chapter 18. Cable Properties and Propagation of Action Potentials

I Summary

II Introduction

III Frequency-Modulated Signals

IV Cable Properties

V Conduction of Action Potentials

VI External Recording of Action Potentials

Appendix 1 Additional Discussion of Input Resistance and Impedance

Appendix 2 Propagation in Cardiac Muscle and Smooth Muscles

AII Some Experimental Facts

AIII Electric Field Model

AIV Electronic Model for Simulation of Propagation

AV PSpice Model for Simulation of Propagation

BIBLIOGRAPHY

Chapter 19. Electrogenesis of Membrane Excitability

I Summary

II Introduction

III Action Potential Characteristics

IV Electrogenesis of Action Potentials

V Effect of Resting Potential on Action Potential

VI Electrogenesis of Afterpotentials

Appendix

AII Additional Information on K+ Channels

AIII Whole-Cell Voltage Clamp

BIBLIOGRAPHY

Chapter 20. Patch-Clamp Techniques

I Introduction

II Applications of the Patch-Clamp Technique

III Patch-Clamp Techniques

IV Data Acquisition

V Current Recordings and Analysis

VI Automated Patch-clamp

Acknowledgments

BIBLIOGRAPHY

Chapter 21. Structure and Mechanism of Voltage-Gated Ion Channels

I Summary

II Introduction: How Is Ion Channel Structure Studied?

III Biochemistry of Ion Channels: Purification and Characterization of Voltage-Gated Channels

IV Channel Structure Investigation through Manipulation of DNA Sequences Encoding Channel Polypeptides

V Molecular Mechanisms of Channel Function: How Does One Investigate Them?

VI Isoforms of Voltage-Gated Channels as Part of a Large Superfamily

VII Future Directions

BIBLIOGRAPHY

Chapter 22. Biology of Gap Junctions

I Introduction

II Advantages of Electrical Synapses in Excitable Cells

III Ubiquitous Membrane Permeable Junctions

IV Structural Candidates for the Permeable Cell Junction

V Ultrastructural Characterization of Gap Junctions and Correlations with Cell Coupling

VI Molecular and Structural Studies of Gap Junction Proteins

VII Two Large Families of Gap Junction Proteins

VIII Channels within Gap Junctions

IX Evidence for Charge Selectivity

X Channel Properties of Different Connexins

XI Gating by Ions and Second Messengers

XII Regulation of Functions of Connexin-Based Gap Junctions at Multiple Levels

XIII Specific Biological Functions of Gap Junctions

XIV Gap Junctions in Human Disease and in Murine Models of Human Disease

In Memoriam

BIBLIOGRAPHY

Chapter 23. Regulation of Cardiac Ion Channels by Cyclic Nucleotide-Dependent Phosphorylation

I Summary

II Introduction

III Regulation of the Cardiac L-type Ca2+ Channels by Cyclic AMP

IV Regulation of the L-type Ca2+ Channels by Cyclic GMP

V Phosphodiesterases

VI Compartmentalization of Cyclic Nucleotides

BIBLIOGRAPHY

Chapter 24. Direct Regulation of Ion Channels by GTP-Binding Proteins

I Introduction

II G-Protein-Coupled Receptors

III The G-Protein Cyclic Reaction Mediates Receptor-to-Channel Signal Transmission

IV Electrophysiological Evidence for K+ Channel Activation by G Proteins

V Electrophysiological Properties of KG Channels

VI Direct Coupling of KG Channel Subunits to Gβγ

VII Structural Basis of the Regulation of KG Channel Activity

VIII RGS Proteins Confer Voltage-Dependent Gating on KG Channel

IX Conclusions

BIBLIOGRAPHY

Chapter 25. Developmental Changes in Ion Channels

I Summary

II Introduction

III Cardiomyocytes

IV Skeletal Muscle Fibers

V Neurons

VI Concluding Remarks

BIBLIOGRAPHY

Chapter 26. Regulation of Ion Channel Localization and Activity Through Interactions with the Cytoskeleton

I Summary

II General Introduction

III Mechanisms for Interactions Between the Cytoskeleton and Ion Channels

IV General Conclusions

BIBLIOGRAPHY

Chapter 27. Why are So Many Ion Channels Mechanosensitive?

I Summary

II Introduction

III Eukaryotic MS Channels – Bilayer Structure, Bilayer Deformation

IV Channel Mechanosensitivity – Tuning of Channel Behavior

V VGCS and the Mechanosensitivity of Discrete Transitions

VI Bilayer Structure in X, Y and Z – One LPP Here, Another LPP There

VII Physiology? Read with Caution. Proceed with Caution

BIBLIOGRAPHY

Section IV Ion Channels as Targets for Toxins, Drugs, and Genetic Diseases

Chapter 28. Ion Channels as Targets for Toxins

I Summary

II Introduction

III Voltage-Gated Sodium Channels (VGSCs; NaV1.x)

IV Voltage-Activated and Ca2+-Activated Potassium Channels

V Voltage-Dependent Calcium Channels

VI Other Toxins and Channels

BIBLIOGRAPHY

Chapter 29. Ion Channels as Targets for Drugs

I Summary

II Calcium Channels

III Sodium (Na+) Channels

BIBLIOGRAPHY

Chapter 30. Inherited Diseases of Ion Transport

I Summary

II Introduction

III Identifying Heritable Mutations Underlying Diseases of Ion Transport

IV Familial Hemiplegic Migraine

V Cystic Fibrosis

VI Long QT Syndrome

VII Myotonia and Periodic Paralysis of Skeletal Muscle

VIII Malignant Hyperthermia

IX Liddle’s Syndrome

X Bartter Syndrome

BIBLIOGRAPHY

Section V Synaptic Transmission and Sensory Transduction

Chapter 31. Ligand-Gated Ion Channels

I Summary

II Introduction

III Classes of Ligand-Gated Ion Channels

IV Basic Physiological Features

V Molecular Structure

VI Neuronal Acetylcholine Receptor Channels

VII γ-Aminobutyric Acid and Glycine Receptor Channels

VIII Glutamate Receptor Channels

BIBLIOGRAPHY

Chapter 32. Synaptic Transmission

I Summary

II Introduction

III Structure and Function of Chemical Synapses: An Overview

IV Neurotransmission

BIBLIOGRAPHY

Chapter 33. Excitation—Secretion Coupling

I Summary

II Introduction

III Cellular Components Involved in Excitation–Secretion Coupling

IV Cellular and Molecular Events in Chromaffin, Mast Cells and Neuronal Synaptic Vesicles

V Hormone Release in Endocrine Cells

Acknowledgments

BIBLIOGRAPHY

Chapter 34. Stimulus—Response Coupling in Metabolic Sensor Cells

I Introduction

II Stimulus–Secretion Coupling in the Pancreatic Islet Cells

III Metabolic Sensing as Protection from Hypometabolic Injury

IV Stimulus–Secretion Coupling in Carotid Chemoreceptor Cells

V Stimulus–Contraction Coupling in Vascular Smooth Muscle Cells

VI Coupling of Oxygen Sensing to Red Cell Production by Erythropoietin-Secreting Cells

Acknowledgments

BIBLIOGRAPHY

Chapter 35. Cyclic Nucleotide-Gated Ion Channels

I Summary

II Introduction

III Physiological Roles and Locations

IV Control by Cyclic Nucleotide Enzyme Cascades

V Functional Properties

VI Molecular Structure

VII Functional Modulation

BIBLIOGRAPHY

Chapter 36. Sensory Receptors and Mechanotransduction

I Introduction

II Sensory Transduction

III Sensory Adaptation

IV Information Transmission by Sensory Receptors

V Mechanoreceptors

VI Experimental Mechanoreceptor Preparations

VII Steps in Mechanoreception

VIII Efferent Control of Mechanoreceptors

IX Conclusions

BIBLIOGRAPHY

Chapter 37. Acoustic Transduction

I Summary

II Introduction

III Mammalian Inner Ear Structure

IV Cell Physiology of Endolymph Homeostasis

V Genetic Basis of Deafness

VI Cell Physiology of Acoustic Transduction

VII Concluding Remarks

Acknowledgment

BIBLIOGRAPHY

Chapter 38. Visual Transduction

I Summary

II Introduction

III Photoreceptor Cells

IV Physiology of Visual Transduction

V Molecular Mechanisms

BIBLIOGRAPHY

Chapter 39. Gustatory and Olfactory Sensory Transduction

I Summary

II Introduction

III Taste Receptor Cells

IV Olfactory Receptor Cells

BIBLIOGRAPHY

Chapter 40. Infrared Sensory Organs

I Summary

II Introduction

III Nature of the Stimulus: What is Infrared (IR) Radiation?

IV Infrared-Sensitive Pit Organs in Snakes

BIBLIOGRAPHY

Chapter 41. Electroreceptors and Magnetoreceptors

I Summary

II Introduction

III Ampullary Electroreceptors

IV Tuberous Electroreceptors

BIBLIOGRAPHY

Section VI Muscle and Other Contractile Systems

Chapter 42. Skeletal Muscle Excitability

I Summary

II Introduction

III General Overview of Electrogenesis of the Action Potential

IV Ion Channel Activation and Inactivation

V Slow Delayed Rectifier K+ Current

VI Mechanisms of Repolarization

VII ATP-Dependent K+ Channels

VIII Electrogenesis of Depolarizing Afterpotentials

IX Ca2+-Dependent Slow Action Potentials

X Developmental Changes in Membrane Properties

XI Electrogenic Na+-K+ Pump Stimulation

XII Slow Fibers

XIII Conduction of the Action Potential

XIV Excitation Delivery to Fiber Interior by Conduction into the T-Tubular System

Appendix

AII More Information on KATP Channels

AIII Further Evidence that the T-Tubules Fire Na+-Dependent APS

AIV Propagation Velocity in a Passive Cable

AV Evidence for T-Tubule Communication with the SR across the Triadic Junction under Some Conditions

AVI Invertebrate Striated Muscle Fibers

BIBLIOGRAPHY

Chapter 43. Cardiac Action Potentials

I Summary

II Introduction

III Resting Membrane Potential

IV Currents During the Action Potential Phases

V Additional Currents Contributing to the Action Potential

VI Regional Differences in Action Potentials

VII Automaticity

VIII Channelopathies

BIBLIOGRAPHY

Chapter 44. Smooth Muscle Excitability

I Introduction

II Determination of Resting Membrane Potential in SMCS

III Potassium Channels

IV Voltage-Dependent Calcium Channels

V Transient Receptor Potential (TRP) Channels

VI Excitation of Gastrointestinal SMCS

VII Airway Smooth Muscle

VIII Concluding Remarks

Acknowledgments

BIBLIOGRAPHY

Chapter 45. Excitation—Contraction Coupling in Skeletal Muscle

I Summary

II Introduction

III Overview of EC Coupling

IV Speed of Skeletal Muscle Activation

V Membrane Architecture of EC Coupling

VI The DHPR Protein

VII The Ryanodine Receptor

VIII Physiological Interactions Between the DHPR and RyR1

Acknowledgment

BIBLIOGRAPHY

Chapter 46. Contraction of Muscles

I Summary

II Introduction

III The Mechanisms of Force Production and Shortening: Muscle Mechanics

IV Muscle Energetics

V Muscle Metabolism

VI Comparative Mechanochemical Function

BIBLIOGRAPHY

Chapter 47. Flagella, Cilia, Actin- and Centrin-based Movement

I Introduction

II Bacterial flagella

III Cilia

IV Non-Muscle Actin

V Biological Springs

VI Cannons

VII A Few Lessons Learned

BIBLIOGRAPHY

Chapter 48. Electrocytes of Electric Fish

I Summary

II Introduction

III Anatomy of Electrophorus and Mechanism of the Electrical Discharge

IV Electrocyte Membrane Electrophysiology

V Comparative Physiology of Electrophorus and Torpedo – Models for Mammalian Excitable Cells

BIBLIOGRAPHY

Section VII Protozoa and Bacteria

Chapter 49. Physiological Adaptations of Protists

I Introduction: Terminology and Phylogeny

II Biophysical Constraints of Scale: the Example of Filter-Feeding

III Nutrition and Excretion

IV Energetic Adaptations: Mitochondria and their Relatives

V Sensory Adaptations, Membrane Potentials and Ion Channels

VI Incorporation of Physiological Units from Other Cells

VII Structures with Unknown Functions

VIII Coordinated Protistan Responses to Gravity and to Gradients of Oxygen and Light: an Example from Physiological Ecology

IX Summary: Protistan Diversity

Acknowledgments

BIBLIOGRAPHY

Chapter 50. Physiology of Prokaryotic Cells

I The Diversity of Prokaryotic Organisms

II Prokaryotic Cytology

III Energetics of Bacterial Cells

IV Solute Transport

V Metabolic Strategies

VI Responding to the Environment

VII The Physiology of Pathogenesis

VIII Prokaryotes Living in Extreme Environments

IX Conclusions

BIBLIOGRAPHY

Section VIII Specialized Processes: Photosynthesis and Bioluminescence

Chapter 51. Photosynthesis

I Summary

II Introduction

III Chloroplasts

IV Biochemistry of Carbon Assimilation

V Formation of ATP

VI Photosynthetic Electron Transport

VII Regulation of Photosynthesis

BIBLIOGRAPHY

Chapter 52. Bioluminescence

I Summary

II Introduction

III What is Bioluminescence? Physical and Chemical Mechanisms

IV Luminous Organisms: Abundance, Diversity and Distribution

V Functions of Bioluminescence

VI Bacterial Luminescence

VII Dinoflagellate Luminescence

VIII Coelenterates and Ctenophores

IX Firefly Luminescence

X Other Organisms: Other Chemistries

XI Applications of Bioluminescence

XII Concluding Remarks

BIBLIOGRAPHY

Appendix: Excitability of Smooth Muscles: Some Basic Facts

I Fast Na+ Channels in Smooth Muscle Cells

II Propagation of Overshooting Action Potentials in Intestinal Smooth Muscle

III Vascular Smooth Muscle: Part 1

IV Vascular Smooth Muscle: Part 2

V High Input Resistance and Short Length Constant

VI Induction of APs by Ba2+ and TEA+

VII Enhancement of the TEA-Induced APS

VIII Excitatory Junction Potentials Sometimes Give Rise to APS: Analogy with Slow Fibers of Skeletal Muscle

IX Electrical Equivalent Circuit for VSM Cells

Index