Quantitative Human Physiology

An Introduction

2nd Edition - December 16, 2016

Author: Joseph J Feher

Hardback ISBN:

9 7 8 - 0 - 1 2 - 8 0 0 8 8 3 - 6

eBook ISBN:

9 7 8 - 0 - 1 2 - 8 0 1 1 5 4 - 6

Quantitative Human Physiology: An Introduction, winner of a 2018 Textbook Excellence Award (Texty), is the first text to meet the needs of the undergraduate bioengineering student… Read more

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Quantitative Human Physiology: An Introduction, winner of a 2018 Textbook Excellence Award (Texty), is the first text to meet the needs of the undergraduate bioengineering student who is being exposed to physiology for the first time, but requires a more analytical/quantitative approach. This book explores how component behavior produces system behavior in physiological systems. Through text explanation, figures, and equations, it provides the engineering student with a basic understanding of physiological principles with an emphasis on quantitative aspects.

Preface
- This Text Is a Physiology Text First, and Quantitative Second
- The Text Uses Mathematics Extensively
- Not All Things Worth Knowing Are Worth Knowing Well
- Perfect Is the Enemy of Good: Equations Aren’t Perfect, but They’re Often Good Enough
- Examples and Problem Sets Allow Application of the Useful Equations
- Learning Objectives, Summaries, and Review Questions Guide Student Learning
- Clinical Applications Pique Interest
- How Instructors Can Use This Text
- Ancillary Materials for Instructors
- How students Can Use This Text
- Ancillary Materials for Students
- Student Feedback
Acknowledgments
Unit 1: Physical and Chemical Foundations of Physiology
- 1.1. The Core Principles of Physiology
  - Abstract
  - Human Physiology Is the Integrated Study of the Normal Function of the Human Body
  - The Body Consists of Causal Mechanisms That Obey the Laws of Physics and Chemistry
  - The Core Principles of Physiology
  - Cells Are the Organizational Unit of Life
  - The Concept of Homeostasis Is a Central Theme of Physiology
  - Evolution Is an Efficient Cause of the Human Body Working Over Longtime Scales
  - Living Beings Transform Energy and Matter
  - Function Follows Form
  - Positive Feedback Control Systems Have Different Signs for the Adjustment to Perturbations
  - We Are Not Alone: the Microbiota
  - Physiology Is a Quantitative Science
  - Summary
  - Review Questions
- 1.2. Physical Foundations of Physiology I: Pressure-Driven Flow
  - Abstract
  - Forces Produce Flows
  - Conservation of Matter or Energy Leads to the Continuity Equation
  - Steady-State Flows Require Linear Gradients
  - Heat, Charge, Solute, and Volume Can Be Stored: Analogues of Capacitance
  - Pressure Drives Fluid Flow
  - Poiseuille’s Law Governs Steady-State Laminar Flow in Narrow Tubes
  - The Law of LaPlace Relates Pressure to Tension in Hollow Organs
  - Summary
  - Review Questions
  - Appendix 1.2.A1 Derivation of Poiseuille’s Law
  - Appendix 1.2.A2 Introductory Statistics and Linear Regresssion
- 1.3. Physical Foundations of Physiology II: Electrical Force, Potential, Capacitance, and Current
  - Abstract
  - Coulomb’s Law Describes Electrical Forces
  - The Electric Potential Is the Work per Unit Charge
  - The Idea of Potential Is Limited to Conservative Forces
  - The Work Done by a Conservative Force Is Path Independent
  - Potential Difference Depends Only on the Initial and Final States
  - The Electric Field Is the Negative Gradient of the Potential
  - Force and Energy Are Simple Consequences of Potential
  - Gauss’s Law Is a Consequence of Coulomb’s Law
  - The Capacitance of a Parallel Plate Capacitor Depends on Its Area and Plate Separation
  - Biological Membranes Are Electrical Capacitors
  - Electric Charges Move in Response to Electric Forces
  - Movement of Ions in Response to Electrical Forces Makes a Current and a Solute Flux
  - The Relationship Between J and C Defines an Average Velocity
  - Ohm’s Law Relates Current to Potential
  - Kirchhoff’s Current Law and Kirchhoff’s Voltage Law
  - The Time Constant Characterizes the Charging of a Capacitor in a Simple RC Circuit
  - Summary
  - Review Questions
- Problem Set 1.1. Physical Foundations: Pressure and Electrical Forces and Flows
- 1.4. Chemical Foundations of Physiology I: Chemical Energy and Intermolecular Forces
  - Abstract
  - Atoms Contain Distributed Electrical Charges
  - Electron Orbitals Have Specific, Quantized Energies
  - Human Life Requires Relatively Few of the Chemical Elements
  - Atomic Orbitals Explain the Periodicity of Chemical Reactivities
  - Atoms Bind Together in Definite Proportions to Form Molecules
  - Compounds Have Characteristic Geometries and Surfaces
  - Single CC Bonds Can Freely Rotate
  - Double CC Bonds Prohibit Free Rotation
  - Chemical Bonds Have Bond Energies, Bond Lengths, and Bond Angles
  - Bond Energy Is Expressed as Enthalpy Changes
  - The Multiplicity of CX Bonds Produces Isomerism
  - Unequal Sharing Makes Polar Covalent Bonds
  - Ionic Bonds Result from Atoms with Highly Unequal Electronegativities
  - Water Provides an Example of a Polar Bond
  - Intermolecular Forces Arise from Electrostatic Interactions
  - Hydrogen Bonding Occurs Between Two Electronegative Centers
  - Dipole–Dipole Interactions Are Effective Only Over Short Distances
  - London Dispersion Forces Involve Induced Dipoles
  - Close Approach of Molecules Results in a Repulsive Force That Combines with the van der Waals Forces in the Lennard–Jones Potential
  - Atoms Within Molecules Wiggle and Jiggle, and Bonds Stretch and Bend
  - Summary
  - Review Questions
  - Appendix 1.4.A1 Dipole Moment
- 1.5. Chemical Foundations of Physiology II: Concentration and Kinetics
  - Abstract
  - Avogadro’s Number Counts the Particles in a Mole
  - Concentration Is the Amount Per Unit Volume
  - Scientific Prefixes Indicate Order of Magnitude
  - Dilution of Solutions Is Calculated Using Conservation of Solute
  - Calculation of Fluid Volumes by the Fick Dilution Principle
  - Chemical Reactions Have Forward and Reverse Rate Constants
  - First-Order Rate Equations Show Exponential Decay
  - Rates of Chemical Reactions Depend on the Activation Energy
  - Enzymes Speed Up Reactions by Lowering E_a
  - The Michaelis–Menten Formulation of Enzyme Kinetics
  - Physiology Is All About Surfaces
  - Summary
  - Review Questions
  - Appendix 1.5.A1 Transition State Theory Explains Reaction Rates in Terms of an Activation Energy
  - Appendix 1.5.A2 Unidirectional Fluxes Over a Series of Intermediates Depend on All of the Individual Unidirectional Fluxes
  - Appendix 1.5.A3 Simple Compartmental Analysis
- 1.6. Diffusion
  - Abstract
  - Fick’s First Law of Diffusion Was Proposed in Analogy to Fourier’s Law of Heat Transfer
  - Fick’s Second Law of Diffusion Follows from the Continuity Equation and Fick’s First Law
  - Fick’s Second Law Can Be Derived from the One-Dimensional Random Walk
  - The Time for One-Dimensional Diffusion Increases with the Square of Distance
  - Diffusion Coefficients in Cells Are Less than the Free Diffusion Coefficient in Water
  - External Forces Can Move Particles and Alter the Diffusive Flux
  - The Stokes–Einstein Equation Relates the Diffusion Coefficient to Molecular Size
  - Summary
  - Review Questions
  - Appendix 1.6.A1 Derivation of Einstein’s Frictional Coefficient from Momentum Transfer in Solution
- 1.7. Electrochemical Potential and Free Energy
  - Abstract
  - Diffusive and Electrical Forces Can Be Unified in the Electrochemical Potential
  - The Overall Force That Drives Flux Is the Negative Gradient of the Electrochemical Potential
  - The Electrochemical Potential Is the Gibbs Free Energy Per Mole
  - The Sign of ΔG Determines the Direction of a Reaction
  - Processes with ΔG>0 Can Proceed Only by Linking Them with Another Process with ΔG<0
  - The Large Negative Free Energy of ATP Hydrolysis Powers Many Biological Processes
  - Measurement of the Equilibrium Concentrations of ADP, ATP, and Pi Allows Us to Calculate ΔG⁰
  - Summary
  - Review Questions
- Problem Set 1.2. Kinetics and Diffusion
Unit 2: Membranes, Transport, and Metabolism
- 2.1. Cell Structure
  - Abstract
  - For Cells, Form Follows Function
  - Organelles Make Up the Cell Like the Organs Make Up the Body
  - The Cell Membrane Marks the Limits of the Cell
  - The Cytosol Provides a Medium for Dissolution and Transport of Materials
  - The Cytoskeleton Supports the Cell and Forms a Network for Vesicular Transport
  - Microtubules Are the Largest Cytoskeletal Filaments
  - Actin Filaments Arise from Nucleation Sites Usually in the Cell Cortex
  - Intermediate Filaments Are Diverse
  - Cytoskeletal Units Form Free-Floating Structures Based on Tensegrity
  - Myosin Interacts with Actin to Produce Force or Shortening
  - The Nucleus Is the Command Center of the Cell
  - Ribosomes Are the Site of Protein Synthesis
  - The ER Is the Site of Protein and Lipid Synthesis and Processing
  - The Golgi Apparatus Packages Secretory Materials
  - The Mitochondrion Is the Powerhouse of the Cell
  - Lysosomes and Peroxisomes Are Bags of Enzymes
  - Proteasomes Degrade Marked Proteins
  - Cells Attach to Each Other Through a Variety of Junctions
  - Summary
  - Review Questions
  - Appendix 2.1.A1 Some Methods for Studying Cell Structure and Function
  - Microscopic Resolution Is the Ability to Distinguish Between Two Separated Objects
  - The Electron Microscope Has Advanced Our Understanding of Cell Structure
  - Subcellular Fractionation Allows Studies of Isolated Organelle But Requires Disruption of Cell Function and Structure
  - Differential Centrifugation Produces Enriched Fractions of Subcellular Organelles
  - Density Gradient Centrifugation Enhances Purity of the Fractions
  - Analysis of Centrifugation Separation
  - Centripetal Force in a Spinning Tube Is Provided by the Solvent
  - The Magnitude of the Centripetal Force Can Be Expressed as Relative Centrifugal Force
  - The Velocity of Sedimentation Is Measured in Svedbergs or S Units
  - Density Gradient Centrifugation
  - Other Optical Methods
- 2.2. DNA and Protein Synthesis
  - Abstract
  - DNA Makes Up the Genome
  - DNA Consists of Two Intertwined Sequences of Nucleotides
  - RNA Is Closely Related to DNA
  - The Genetic Code Is a System Property
  - Regulation of DNA Transcription Defines the Cell Type
  - The Histone Code Provides Another Level of Regulation of Gene Transcription
  - DNA Methylation Represses Transcription
  - Summary
  - Review Questions
- 2.3. Protein Structure
  - Abstract
  - Amino Acids Make Up Proteins
  - Hydrophobic Interactions Can Be Assessed from the Partition Coefficient
  - Peptide Bonds Link Amino Acids Together in Proteins
  - Protein Function Centers on Their Ability to Form Reactive Surfaces
  - There Are Four Levels of Description for Protein Structure
  - Posttranslational Modification Regulates and Refines Protein Structure and Function
  - Protein Activity Is Regulated by the Number of Molecules or by Reversible Activation/Inactivation
  - Summary
  - Review Questions
- 2.4. Biological Membranes
  - Abstract
  - Biological Membranes Surround Most Intracellular Organelles
  - Biological Membranes Consist of a Lipid Bilayer Core with Embedded Proteins and Carbohydrate Coats
  - Organic Solvents Can Extract Lipids from Membranes
  - Biological Membranes Contain Mostly Phospholipids
  - Phospholipids Contain Fatty Acyl Chains, Glycerol, Phosphate, and a Hydrophilic Group
  - Plasmanyl Phospholipids and Plasmenyl Phospholipids Use Fatty Alcohols Instead of Fatty Acids
  - Sphingolipids Use Sphingosine as a Backbone and Are Particularly Rich in Brain and Nerve Tissues
  - Other Lipid Components of Membranes Include Cardiolipin, Sphingolipids, and Cholesterol
  - Surface Tension of Water Results from Asymmetric Forces at the Interface
  - Water “Squeezes Out” Amphipathic Molecules
  - Amphipathic Molecules Spread Over a Water Surface, Reduce Surface Tension, and Produce an Apparent Surface Pressure
  - Phospholipids Form Bilayer Membranes Between Two Aqueous Compartments
  - Lipid Bilayers Can Also Form Liposomes
  - Although Lipids Form the Core, Membrane Proteins Carry Out Many of the Functions of Membranes
  - Membrane Proteins Bind to Membranes with Varying Affinity
  - Lipids Maintain Dynamic Motion Within the Bilayer
  - Lipid Rafts Are Special Areas of Lipid and Protein Composition
  - Caveolae and Clathrin-Coated Pits Are Stabilized by Integral Proteins
  - Secreted Proteins Have Special Mechanisms for Getting Inside the Endoplasmic Reticulum
  - Summary
  - Review Questions
- Problem Set 2.1. Surface Tension, Membrane Surface Tension, Membrane Structure, Microscopic Resolution, and Cell Fractionation
- 2.5. Passive Transport and Facilitated Diffusion
  - Abstract
  - Membranes Possess a Variety of Transport Mechanisms
  - A Microporous Membrane Is One Model of a Passive Transport Mechanism
  - Dissolution in the Lipid Bilayer Is Another Model for Passive Transport
  - Facilitated Diffusion Uses a Membrane-Bound Carrier
  - Facilitated Diffusion Saturates with Increasing Solute Concentrations
  - Facilitated Diffusion Shows Specificity
  - Facilitated Diffusion Shows Competitive Inhibition
  - Passive Transport Occurs Spontaneously Without Input of Energy
  - Ions Can be Passively Transported Across Membranes by Ionophores or by Channels
  - Ionophores Carry Ions Across Membranes or Form Channels
  - Ion Channels
  - Water Moves Passively Through Aquaporins
  - Summary
  - Review Questions
- 2.6. Active Transport: Pumps and Exchangers
  - Abstract
  - The Electrochemical Potential Difference Measures the Energetics of Ion Permeation
  - Active Transport Mechanisms Link Metabolic Energy to Transport of Materials
  - Na,K-ATPase Is an Example of Primary Active Transport
  - Na,K-ATPase Forms a Phosphorylated Intermediate
  - The Na,K-ATPase Is Electrogenic
  - There Are Many Different Primary Active Transport Pumps
  - The Na–Ca Exchanger as an Example of Secondary Active Transport
  - Secondary Active Transport Mechanisms Are Symports or Antiports
  - Summary
  - Review Questions
  - Appendix 2.6.A1 Derivation of the Ussing Flux Ratio Equation
  - Appendix 2.6.A2 Nomenclature of Transport Proteins
  - Carrier Classifications
  - Solute Carriers
  - ATP-Driven Ion Pumps
  - ABC Transporters
  - Aquaporins
- 2.7. Osmosis and Osmotic Pressure
  - Abstract
  - Osmosis Is the Flow of Water Driven by Solute Concentration Differences
  - The van’t Hoff Equation Relates Osmotic Pressure to Concentration
  - Thermodynamic Derivation of van’t Hoff’s Law
  - Osmotic Pressure Is a Property of Solutions Related to Other Colligative Properties
  - The Osmotic Coefficient φ Corrects for the Assumption of Dilute Solution and for Nonideal Behavior
  - The Rational Osmotic Coefficient Corrects for the Assumption of Ideality
  - Equivalence of Osmotic and Hydrostatic Pressures
  - The Reflection Coefficient Corrects van’t Hoff’s Equation for Permeable Solutes
  - L_p for a Microporous Membrane Depends on the Microscopic Characteristics of the Membrane
  - Case 1: The Solute Is Very Small Compared to the Pore
  - Case 2: The Solute Is Larger than the Pore: The Mechanism of Osmosis for Microporous Membranes
  - Case 3: The Reflection Coefficient Results from Partially Restricted Entry of Solutes into the Pores
  - Solutions May Be Hypertonic or Hypotonic
  - Osmosis, Osmotic Pressure, and Tonicity Are Related But Distinct Concepts
  - Cells Behave Like Osmometers
  - Cells Actively Regulate Their Volume Through RVDs and RVIs
  - Summary
  - Review Questions
  - Appendix 2.7.A1 Mechanism of Osmosis: Filtration Versus Diffusion Down a Concentration Gradient
- Problem Set 2.2. Membrane Transport
- 2.8. Cell Signaling
  - Abstract
  - Signaling Transduces One Event into Another
  - Cell-to-Cell Communication Can Also Use Direct Mechanical, Electrical, or Chemical Signals
  - Signals Elicit a Variety of Classes of Cellular Responses
  - Electrical Signals and Neurotransmitters Are Fastest; Endocrine Signals Are Slowest
  - Voltage-Gated Ion Channels Convey Electrical Signals
  - Voltage-Gated Ca²⁺ Channels Transduce an Electrical Signal to an Intracellular Ca²⁺ Signal
  - Ligand-Gated Ion Channels Open Upon Binding with Chemical Signals
  - Heterotrimeric G-Protein-Coupled Receptors (GPCRs) Are Versatile
  - There Are Four Classes of G-Proteins: Gα_s, Gα_i/Gα_o, Gα_q, and Gα₁₂/Gα₁₃
  - The Response of a Cell to a Chemical Signal Depends on the Receptor and Its Effectors
  - Chemical Signals Can Bind to and Directly Activate Membrane-Bound Enzymes
  - Many Signals Alter Gene Expression
  - Nuclear Receptors Alter Gene Transcription
  - Nuclear Receptors Recruit Histone Acetylase to Unwrap the DNA from the Histones
  - Nuclear Receptors Recruit Transcription Factors
  - Other Signaling Pathways Also Regulate Gene Expression
  - Summary of Signaling Mechanisms
  - Summary
  - Review Questions
- 2.9. ATP Production I: Glycolysis
  - Abstract
  - Take a Global View of Metabolism
  - Energy Production Occurs in Three Stages: Breakdown into Units, Formation of Acetyl CoA, and Complete Oxidation of Acetyl CoA
  - ATP Is the Energy Currency of the Cell
  - Fuel Reserves Are Stored in the Body Primarily in Fat Depots and Glycogen
  - Glucose Is a Readily Available Source of Energy
  - Glucose Release by the Liver Is Controlled by Hormones Through a Second Messenger System
  - The Liver Exports Glucose into the Blood Because It Can Dephosphorylate Glucose-6-P
  - A Specific Glucose Carrier Takes Glucose up into Cells
  - Glycolysis Is a Series of Biochemical Transformations Leading from Glucose to Pyruvate
  - Glycolysis Generates ATP Quickly in the Absence of Oxygen
  - Glycolysis Requires NAD⁺
  - Gluconeogenesis Requires Reversal of Glycolysis
  - Summary
  - Review Questions
- 2.10. ATP Production II: The TCA Cycle and Oxidative Phosphorylation
  - Abstract
  - Oxidation of Pyruvate Occurs in the Mitochondria via the TCA Cycle
  - Pyruvate Enters the Mitochondria and Is Converted to Acetyl CoA
  - Pyruvate Dehydrogenase Releases CO₂ and Makes NADH
  - The Affinity of a Chemical for Electrons Is Measured by Its Standard Reduction Potential
  - The Reduction Potential Depends on the Concentration of Oxidized and Reduced Forms, and the Temperature
  - The TCA Cycle Is a Catalytic Cycle
  - The ETC Links Chemical Energy to H⁺ Pumping Out of the Mitochondria
  - Oxygen Accepts Electrons at the End of the ETC
  - Proton Pumping and Electron Transport Are Tightly Coupled
  - The ATP Synthase Couples Inward H⁺ Flux to ATP Synthesis
  - The Proton Electrochemical Gradient Provides the Energy for ATP Synthesis
  - NADH Forms About 2.5 ATP Molecules; FADH₂ Forms About 1.5 ATP Molecules
  - ATP Can Be Produced From Cytosolic NADH
  - Most of the ATP Produced During Complete Glucose Oxidation Comes from Oxidative Phosphorylation
  - Mitochondria Have Specific Transport Mechanisms
  - Summary
  - Review Questions
- 2.11. ATP Production III: Fatty Acid Oxidation and Amino Acid Oxidation
  - Abstract
  - Fats and Proteins Contribute 50% of the Energy Content of Many Diets
  - Depot Fat Is Stored as Triglycerides and Broken Down to Glycerol and Fatty Acids for Energy
  - Glycerol Is Converted to an Intermediate of Glycolysis
  - Fatty Acids Are Metabolized in the Mitochondria and Peroxisomes
  - Beta Oxidation Cleaves Two Carbon Pieces off Fatty Acids
  - The Liver Packages Substrates for Energy Production by Other Tissues
  - Amino Acids Can Be Used to Generate ATP
  - Amino Acids Are Deaminated to Enable Oxidation
  - Urea Is Produced During Deamination and Is Eliminated as a Waste Product
  - Summary
  - Review Questions
Unit 3: Physiology of Excitable Cells
- 3.1. The Origin of the Resting Membrane Potential
  - Abstract
  - Introduction
  - The Equilibrium Potential Arises from the Balance Between Electrical Force and Diffusion
  - The Equilibrium Potential for K⁺ Is Negative
  - Integration of the Nernst–Planck Electrodiffusion Equation Gives the Goldman–Hodgkin–Katz Equation
  - Slope Conductance and Chord Conductance Relate Ion Flows to the Net Driving Force
  - The Chord Conductance Equation Relates Membrane Potential to All Ion Flows
  - The Current Convention Is that an Outward Current Is Positive
  - Summary
  - Review Questions
  - Appendix 3.1.A1 Derivation of the GHK Equation
- 3.2. The Action Potential
  - Abstract
  - Cells Use Action Potentials as Fast Signals
  - The Motor Neuron Has Dendrites, a Cell Body, and an Axon
  - Passing a Current Across the Membrane Changes the Membrane Potential
  - An Outward Current Hyperpolarizes the Membrane Potential
  - The Result of Depolarizing Stimulus of Adequate Size Is a New Phenomenon—the Action Potential
  - The Action Potential Is All or None
  - The Latency Decreases with Increasing Stimulus Strength
  - Threshold Is the Membrane Potential at Which an Action Potential Is Elicited 50% of the Time
  - The Nerve Cannot Produce a Second Excitation During the Absolute Refractory Period
  - The Action Potential Reverses to Positive Values, Called the Overshoot
  - The Strength–Duration Relationship is Hyperbolic
  - Voltage-Dependent Changes in Ion Conductance Cause the Action Potential
  - The Action Potential Is Accompanied by Na⁺ Influx
  - The Chord Conductance Equation Predicts that Changes in Conductance Will Change the Membrane Potential
  - g_Na Increases Transiently During the Action Potential; g_K Increases Later and Stays Elevated Longer
  - Conductance and Equilibrium Potentials for Na⁺ and K⁺ Account for All of the Features of the Action Potential
  - g_Na Is a Function of a Na⁺-Selective Channel
  - The Inactivation Gates Must Be Reset Before Another Action Potential Can Be Fired
  - Conductance Depends on the Number and State of the Channels
  - Patch Clamp Experiments Measure Unitary Conductances
  - The Current–Voltage Relationship for the Whole Cell Determines the Threshold for Excitation
  - Threshold Depolarization Requires a Threshold Charge Movement, Which Explains the Strength–Duration Relationship
  - The Amount of Charge Necessary to Reach Threshold Explains the Strength–Duration Relationship
  - Summary
  - Review Questions
  - Appendix 3.2.A1 The Hodgkin–Huxley Model of the Action Potential
  - The HH Model Divides the Total Current into Separate Na⁺, K⁺, and Leak Currents
  - The HH Model of the K⁺ Conductance Incorporates Four Independent “Particles”
  - The HH Model of Na⁺ Conductances Uses Activating and Inactivating Particles
  - Calculation of g_Na(t) and g_K(t) for a Voltage Clamp Experiment
  - Results of the Calculations
- 3.3. Propagation of the Action Potential
  - Abstract
  - The Action Potential Moves Along the Axon
  - The Velocity of Nerve Conduction Varies Directly with the Axon Diameter
  - The Action Potential Is Propagated by Current Moving Axially Down the Axon
  - The Time Course and Distance of Electrotonic Spread Depend on the Cable Properties of the Nerve
  - Capacitance Depends on the Area, Thickness, and Dielectric Constant
  - Charge Buildup or Depletion from a Capacitor Constitutes a Capacitative Current
  - The Transmembrane Resistance Depends on the Area of the Membrane
  - The Axoplasmic Resistance Depends on the Distance, Area, and Specific Resistance
  - The Extracellular Resistance Also Depends on the Distance, Area, and Specific Resistance
  - Cable Properties Define a Space Constant and a Time Constant
  - The Cable Properties Explain the Velocity of Action Potential Conduction
  - Saltatory Conduction Refers to the “Jumping” of the Current from Node to Node
  - The Action Potential Is Spread out Over More than One Node
  - Summary
  - Review Questions
  - Appendix 3.3.A1 Capacitance of a Coaxial Capacitor
  - The Capacitance of a Coaxial Cable
- Problem Set 3.1. Membrane Potential, Action Potential, and Nerve Conduction
- 3.4. Skeletal Muscle Mechanics
  - Abstract
  - Muscles Either Shorten or Produce Force
  - Muscles Perform Diverse Functions
  - Muscles Are Classified According to Fine Structure, Neural Control, and Anatomical Arrangement
  - Isometric Force Is Measured While Keeping Muscle Length Constant
  - Muscle Force Depends on the Number of Motor Units That Are Activated
  - The Size Principle States That Motor Units Are Recruited in the Order of Their Size
  - Muscle Force Can Be Graded by the Frequency of Motor Neuron Firing
  - Muscle Force Depends on the Length of the Muscle
  - Recruitment Provides the Greatest Gradation of Muscle Force
  - Muscle Fibers Differ in Contractile, Metabolic and Proteomic Characteristics
  - Motor Units Contain a Single Type of Muscle Fiber
  - The Innervation Ratio of Motor Units Produces a Proportional Control of Muscle Force
  - Muscle Force Varies Inversely with Muscle Velocity
  - Muscle Power Varies with the Load and Muscle Type
  - Eccentric Contractions Lengthen the Muscle and Produce More Force
  - Concentric, Isometric, and Eccentric Contractions Serve Different Functions
  - Muscle Architecture Influences Force and Velocity of the Whole Muscle
  - Muscles Decrease Force Upon Repeated Stimulation; This Is Fatigue
  - Summary
  - Review Questions
- 3.5. Contractile Mechanisms in Skeletal Muscle
  - Abstract
  - Introduction
  - Muscle Fibers Have a Highly Organized Structure
  - The Sliding Filament Hypothesis Explains the Length–Tension Curve
  - Force Is Produced by an Interaction Between Thick Filament Proteins and Thin Filament Proteins
  - The Thin Filament Consists Primarily of Actin
  - α-Actinin at the Z-disk Joins Actin Filaments of Adjacent Sarcomeres
  - Myomesin Joins Thick Filaments at the M-Line or M-Band
  - Overall Structure of the Sarcomere Is Complicated
  - Cross-Bridges from the Thick Filament Split ATP and Generate Force
  - Myosin Heads Are Independent But May Cooperate Through Strain on the Cross-Bridge
  - Cross-Bridge Cycling Rate Explains the Fiber-Type Dependence of the Force–Velocity Curve
  - Force Is Transmitted Outside the Cell Through the Cytoskeleton and Special Transmembrane Proteins
  - Summary
  - Review Questions
- 3.6. The Neuromuscular Junction and Excitation–Contraction Coupling
  - Abstract
  - Motor Neurons Are the Sole Physiological Activators of Skeletal Muscles
  - The Motor Neuron Receives Thousands of Inputs from Other Cells
  - Postsynaptic Potentials Can Be Excitatory or Inhibitory
  - Postsynaptic Potentials Are Graded, Spread Electrotonically, and Decay with Time
  - Action Potentials Originate at the Initial Segment or Axon Hillock
  - Motor Neurons Integrate Multiple Synaptic Inputs to Initiate Action Potentials
  - The Action Potential Travels Down the Axon Toward the Neuromuscular Junction
  - The Neuromuscular Junction Consists of Multiple Enlargements Connected by Axon Segments
  - Neurotransmission at the Neuromuscular Junction Is Unidirectional
  - Motor Neurons Release Acetylcholine to Excite Muscles
  - Ca²⁺ Efflux Mechanisms in the Presynaptic Cell Shut Off the Ca²⁺ Signal
  - Acetylcholine Is Degraded and Then Recycled
  - The Action Potential on the Muscle Membrane Propagates Both Ways on the Muscle
  - The Muscle Fiber Converts the Action Potential into an Intracellular Ca²⁺ Signal
  - The Ca²⁺ during E–C Coupling Originates from the Sarcoplasmic Reticulum
  - Ca²⁺ Release from the SR and Reuptake by the SR Requires Several Proteins
  - Reuptake of Ca²⁺ by the SR Ends Contraction and Initiates Relaxation
  - Cross-Bridge Cycling Is Controlled by Myoplasmic [Ca²⁺]
  - Sequential SR Release and Summation of Myoplasmic [Ca²⁺] Explains Summation and Tetany
  - The Elastic Properties of the Muscle Are Responsible for the Waveform of the Twitch
  - Repetitive Stimulation Causes Repetitive Ca²⁺ Release from the SR and Wave Summation
  - Summary
  - Review Questions
  - Appendix 3.6.A1 Molecular Machinery of the Neuromuscular Junction
  - Appendix 3.6.A2 Molecular Machinery of the Calcium Release Unit
- 3.7. Muscle Energetics, Fatigue, and Training
  - Abstract
  - Muscular Activity Relies on the Free Energy of ATP Hydrolysis
  - Muscular Activity Consumes ATP at High Rates
  - The Aggregate Rate and Amount of ATP Consumption Varies with the Intensity and Duration of Exercise
  - In Repetitive Exercise, Intensity Increases Frequency and Reduces Rest Time
  - Metabolic Pathways Regenerate ATP on Different Timescales and with Different Capacities
  - The Metabolic Pathways Used by Muscle Varies with Intensity and Duration of Exercise
  - At High Intensity of Exercise, Glucose and Glycogen Are the Preferred Fuel for Muscle
  - Lactic Acid Produced by Anaerobic Metabolism Allows High Glycolytic Flux
  - Muscle Fibers Differ in Their Metabolic Properties
  - Blood Lactate Levels Rise Progressively with Increases in Exercise Intensity
  - Mitochondria Import Lactic Acid, Then Metabolize it; This Forms a Carrier System for NADH Oxidation
  - Lactate Shuttles to the Mitochondria, Oxidative Fibers, or Liver
  - The “Anaerobic Threshold” Results from a Mismatch of Lactic Acid Production and Oxidation
  - Exercise Increases Glucose Transporters in the Muscle Sarcolemma
  - Fatigue Is a Transient Loss of Work Capacity Resulting from Preceding Work
  - Initial Training Gains Are Neural
  - Muscle Strength Depends on Muscle Size
  - Endurance Training Uses Repetitive