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Table of Contents


SECTION I	FUNDAMENTAL PHYSICOCHEMICAL CONCEPTS
Chapter 1	Introduction: Homeostasis and Cellular Physiology	1
	Homeostasis Enables the Body to Survive in Diverse Environments	1
	The Body is an Ensemble of Functionally and Spatially Distinct Compartments	2
	The Biological Membranes that Surround Cells and Subcellular Organdies are Lipid Bilayers	2
	Biomembranes are Formed Primarily from Phospholipids But may Also Contain Cholesterol and Sphingolipids	3
	Biomembranes are Not Uniform Structures	3
	Transport Processes are Essential to Physiological Function	4
	Cellular Physiology Focuses on Membrane-Mediated Processes and on Muscle Function	4
	Summary	5
	Keywords and Concepts	5
Chapter 2	Diffusion and Permeability	7
	Diffusion Ts the Migration of Molecules Down a Concentration Gradient	7
	Fick�s First Law of Diffusion Summarizes Our Intuitive Understanding of Diffusion	7
	Essential Aspects of Diffusion are Revealed by Quantitative Examination of Random, Microscopic Movements of Molecules	9
	Random Movements Result in Meandering	9
	The Root-Mean-Squared Displacement is a Good Measure of the Progress of Diffusion	10
	Square-Root-Of-Time Dependence Makes Diffusion Ineffective for Transporting Molecules Over Large Distances	10
	Diffusion Constrains Cell Biology and Physiology	11
	Fick�s First Law can be Used to Describe Diffusion Across a Membrane Barrier	11
	The Net Flux through a Membrane is the Result of Balancing Influx Against Efflux	14
	The Permeability Determines How Rapidly a Solute can be Transported through a Membrane	14
	Summary	18
	Keywords and Concepts	18
	Study Problems	18
Chapter 3	Osmotic Pressure and Water Movement	19
	Osmosis is the Transport of Solvent Driven by a Difference in Solute Concentration Across a Membrane that is Impermeable to Solute	19
	Water Transport during Osmosis Leads to Changes in Volume	20
	Osmotic Pressure Drives the Net Transport Ofwater during Osmosis	20
	Osmotic Pressure and Hydrostatic Pressure are Functionally Equivalent in their Ability to Drive Water Movement through a Membrane	22
	The Direction of Fluid Flow through the Capillary Wall is Determined by the Balance of Hydrostatic and Osmotic Pressures as Described by the Starling Equation	23
	Only Impermeant Solutes can have Permanent Osmotic Effects	27
	Transient Changes in Cell Volume Occur in Response to Changes in the Extracellular Concentration Ofpermeant Solutes	27
	Persistent Changes in Cell Volume Occur in Response to Changes in the Extracellular Concentration of Impermeant Solutes	29
	The Amount of Impermeant Solute Inside the Cell Determines the Cell Volume	29
	Summary	31
	Keywords and Concepts	32
	Study Problems	32
Chapter 4	Electrical Consequences of Ionic Gradients	33
	Ions are Typically Present at Different Concentrations on Opposite Sides of a Biomembrane	33
	Selective Ionic Permeability Through Membranes has Electrical Consequences: the Nernst Equation	33
	The Stable Resting Membrane Potential in a Living Cell is Established by Balancing Multiple Ionic Fluxes	37
	Cell Membranes are Permeable to Multiple Ions	37
	The Resting Membrane Potential can be Quantitatively Estimated by Using the Goldman-Hodgkin- Katz Equation	39
	A Permeant Ion Already in Electrochemical Equilibrium Does Not Need to be Included in the Goldman-Hodgkin-Katz Equation	41
	The Nernst Equation may be Viewed as a Special Case of the Goldman- Hodgkin-Katz Equation	41
	E_K is the �Floor� and the E_Na is the �Ceiling� of Membrane Potential	42
	The Difference Between the Membrane Potential and the Equilibrium Potential of an Ion Determines the Direction of Ion Flow	42
	The Cell can Change its Membrane Potential by Selectively Changing Membrane Permeability to Certain Ions	42
	The Donnan Effect is an Osmotic Threat to Living Cells	43
	Summary	45
	Keywords and Concepts	46
	Study Problems	46
SECTION II	ION CHANNELS AND EXCITABLE MEMBRANES
Chapter 5	Ion Channels	47
	Ion Channels are Critical Determinants of the Electrical Behavior of Membranes	47
	Distinct Types of Ion Channels have Several Common Properties	48
	Ion Channels Increase the Permeability of the Membrane to Ions	48
	Ion Channels are Integral Membrane Proteins that Form Gated Pores	49
	Ion Channels Exhibit Ionic Selectivity	49
	Ion Channels Share Structural Similarities and can be Grouped into Gene Families	50
	Channel Structure is Studied with Biochemical and Molecular Biological Techniques	50
	Structural Details of a K+ Channel are Revealed by X-ray Crystallography	51
	Summary	54
	Key Words and Concepts	54
	Study Problems	54
Chapter 6	Passive Electrical Properties of Membranes	55
	The Time Course and Spread of Membrane Potential Changes are Predicted by the Passive Electrical Properties of the Membrane	55
	The Equivalent Circuit of a Membrane has a Resistor in Parallel with a Capacitor	56
	Membrane Conductance is Established by Open Ion Channels	56
	Capacitance Reflects the Ability of the Membrane to Separate Charge	56
	Passive Membrane Properties Produce Linear Current-Voltage Relationships	57
	Membrane Capacitance Affects the Time Course of Voltage Changes	57
	Ionic and Capacitive Currents Flow when a Channel Opens	57
	The Exponential Time Course of the Membrane Potential can be Understood in Terms of the Passive Properties of the Membrane	59
	Membrane and Axoplasmic Resistances Affect the Passive Spread of Subthreshold Electrical Signals	60
	The Decay of Subthreshold Potentials with Distance can be Understood in Terms of the Passive Properties of the Membrane	61
	The Length Constant is a Measure of How Far Away from a Stimulus Site a Membrane Potential Change will be Detectable	63
	Summary	63
	Keywords and Concepts	64
	Study Problems	64
Chapter 7	Generation and Propagation of the Action Potential	67
	The Action Potential is a Rapid and Transient Depolarization of the Membrane Potential in Electrically Excitable Cells	67
	Properties of Action Potentials can be Studied with Intracellular Microelectrodes	67
	Ion Channel Function is Studied with a Voltage Clamp	69
	Ionic Currents are Measured at a Constant Membrane Potential with a Voltage Clamp	69
	Ionic Currents are Dependent on Voltage and Time	71
	Voltage-Gated Channels Exhibit Voltage-Dependent Conductances	72
	Individual Ion Channels have Two Conductance Levels	74
	Na⁺ Channels Inactivate During Maintained Depolarization	75
	Action Potentials are Generated by Voltage- Gated Na⁺ and K⁺ Channels	76
	The Equivalent Circuit of a Patch of Membrane can be Used to Describe Action Potential Generation	76
	The Action Potential is a Cyclical Process of Channel Opening and Closing	78
	Both Na⁺ Channel Inactivation and Open Voltage-Gated K⁺ Channels Contribute to the Refractory Period	79
	Pharmacological Agents that Block Na⁺ or K⁺ Channels, or Interfere with Na⁺ Channel Inactivation, Alter the Shape of the Action Potential	79
	Action Potential Propagation Occurs as a Result of Local Circuit Currents	80
	In Nonmyelinated Axons an Action Potential Propagates as a Continuous Wave of Excitation Away from the Initiation Site	80
	Conduction Velocity is Influenced by the Time Constant, by the Length Constant, and by Na+ Current Amplitude and Kinetics	81
	Myelination Increases Action Potential Conduction Velocity	82
	Summary	84
	Key Words and Concepts	84
	Study Problems	84
Chapter 8	Ion Channel Diversity	87
	Various Types of Ion Channels Help to Regulate Cellular Processes	87
	Voltage-Gated Ca²⁺ Channels Contribute to Electrical Activity and Mediate Ca²⁺ Entry into Cells	87
	Ca²⁺ Currents can be Recorded with a Voltage Clamp	88
	Ca²⁺ Channel Blockers are Useful Therapeutic Agents	90
	Many Members of the Transient Receptor Potential Superfamily of Channels Mediate Ca²⁺ Entry	91
	Some Members of the Trpc Family are Receptor-Operated Channels	91
	K⁺ -Selective Channels are the Most Diverse Type of Channel	92
	Neuronal K⁺ Channel Diversity Contributes to the Regulation of Action Potential Firing Patterns	92
	Rapidly Inactivating Voltage-Gated K⁺ Channels Cause Delays in Action Potential Generation	93
	Ca²⁺-Activated K⁺ Channels are Opened by Intracellular Ca²⁺	95
	Atp-Sensitive K⁺ Channels are Involved in Glucose-Induced Insulin Secretion from Pancreatic Fi-Cells	95
	A Voltage-Gated K⁺ Channel Helps to Repolarize the Cardiac Action Potential	97
	Ion Channel Activity can be Regulated by Second-Messenger Pathways	97
	b-Adrenergic Receptor Activation Modulates L-Type Ca²⁺ Channels in Cardiac Muscle	99
	Summary	99
	Keywords and Concepts	100
	Study Problems	100
SECTION III	SOLUTE TRANSPORT
Chapter 9	Electrochemical Potential Energy and Transport Processes	103
	Electrochemical Potential Energy Drives All Transport Processes	103
	The Relationship Between Force and Potential Energy is Revealed by Examining Gravity	103
	A Gradient in Chemical Potential Energy Gives Rise to a Chemical Force that Drives the Movement of Molecules	104
	An Ion can have Both Electrical and Chemical Potential Energy	104
	The Nernst Equation is a Simple Manifestation of the Electrochemical Potential	104
	How to Use the Electrochemical Potential to Analyze Transport Processes	108
	Summary	111
	Key Words and Concepts	111
	Study Problems	111
Chapter 10	Passive Solute Transport	113
	Diffusion Across Biological Membranes is Limited by Lipid Solubility	113
	Channel, Carrier, and Pump Proteins Mediate Transport Across Biological Membranes	114
	Transport through Channels is Relatively Fast	114
	Channel Density Controls the Membrane Permeability to a Substance	115
	The Rate of Transport through Open Channels Depends on the Net Driving Force	115
	Transport of Substances through Some Channels is Controlled by �Gating� the Opening and Closing of the Channels	115
	Carriers are Integral Membrane Proteins that Open to Only One Side of the Membrane at a Time	115
	Carriers Facilitate Transport through Membranes	116
	Transport by Carriers Exhibits Kinetic Properties Similar to those of Enzyme Catalysis	116
	Coupling the Transport of One Solute to the �Downhill� Transport of Another Solute Enables Carriers to Move the Cotransported or Countertransported Solute �Uphill� Against an Electrochemical Gradient	119
	Na⁺/H⁺ Exchange is an Example of Na⁺-Coupled Countertransport	119
	Na⁺ is Co Transported with a Variety of Solutes Such as Glucose and Amino Acids	119
	How Does the Electrochemical Gradient for One Solute Affect the Gradient Fora Cotransportedsolute?	121
	Glucose Uptake Efficiency can be Increased by a Change in the Na⁺-Glucose Coupling Ratio	121
	Net Transport of Some Solutes Across Epithelia is Effected by Coupling Two Transport Processes in Series	122
	Various Inherited Defects of Glucose Transport have been Identified	122
	Na⁺ is Exchanged for Solutes Such as Ca²⁺ and H⁺ by Countertransport Mechanisms	123
	Na⁺/Ca²⁺ Exchange is an Example of Coupled Countertransport	124
	Na⁺/Ca²⁺ Exchange is Influenced by Changes in the Membrane Potential	125
	Na⁺/Ca²⁺ Exchange is Regulated by Several Different Mechanisms	125
	Intracellular Ca²⁺ Plays Many Important Physiological Roles	126
	Multiple Transport Systems can be Functionally Coupled	126
	Tertiary Active Transport	129
	Summary	130
	Keywords and Concepts	130
	Study Problems	131
Chapter 11	Active Transport	133
	Primary Active Transport Converts the Chemical Energy from Atp into Electrochemical Potential Energy Stored in Solute Gradients	133
	Three Broad Classes Of ATPases are Involved in Active Ion Transport	133
	The Plasma Membrane Na⁺ Pump (Na⁺, K⁺-ATPase) Maintains the Low Na⁺ and High K⁺ Concentrations in the Cytosol	134
	Nearly All Animal Cells Normally Maintain a High Intracellular K+ Concentration and a Low Intracellular Na+ Concentration	134
	The Na⁺ Pump Hydrolyzes ATP While Transporting Na+ Out of the Cell and K⁺ into the Cell	134
	The Na⁺ Pump is �Electrogenic�	135
	The Na⁺ Pump is the Receptor for Cardiotonic Steroids Such as Ouabain Anddigoxin	135
	Intracellular Ca²⁺ Signaling is Universal and is Closely Tied to Ca²⁺ Homeostasis	136
	Ca²⁺ Storage in the Sarcoplasmic/ Endoplasmic Reticulum is Mediated by a Ca²⁺-Atpase	139
	SERCA has Three Isoforms	139
	The Plasma Membrane of Most Cells has an ATP-Driven Ca²⁺ Pump	140
	The Roles of the Several Ca²⁺ Transporters Differ in Different Cell Types	140
	Different Distributions of the NCX and PMCA in the Plasma Membrane Underlie their Different Functions	140
	Several Other Plasma Membrane Transport ATPases are Physiologically Important	141
	H⁺, K⁺-Atpase Mediates Gastric Acid Secretion	141
	Two Cu²⁺-Transporting ATPases Play Essential Physiological Roles	142
	ATP-Binding Cassette Transporters are a Superfamily of P-Type ATPases	144
	Net Transport Across Epithelial Cells Depends on the Coupling of Apical and Basolateral Membrane Transport Systems	145
	Epithelia are Continuous Sheets of Cells	145
	Epithelia Exhibit Great Functional Diversity	145
	What are the Sources of Na⁺ for Apical Membrane Na⁺- Coupled Solute Transport?	147
	Absorption of Cl^� Occurs by Several Different Mechanisms	148
	Substances can Also be Secreted by Epithelia	149
	Net Water Flow is Coupled to Net Solute Flow Across Epithelia	150
	Summary	153
	Keywords and Concepts	153
	Study Problems	154
SECTION IV	PHYSIOLOGY OF SYNAPTIC TRANSMISSION
Chapter 12	Synaptic Physiology I	155
	The Synapse is a Junction between Cells that is Specialized for Cell-Cell Signaling	155
	Synaptic Transmission can be Either Electrical or Chemical	156
	Electrical Synapses are Designed for Rapid Synchronous Transmission	156
	Most Synapses are Chemical Synapses	157
	Neurons Communicate with Other Neurons and with Muscle by Releasing Neurotransmitters	159
	The Neuromuscular Junction is a Large Chemical Synapse	160
	Transmitter Release at Chemical Synapses Occurs in Multiples of a Unit Size	162
	Ca²⁺ Ions Play an Essential Role in Transmitter Release	164
	The Synaptic Vesicle Cycle is a Precisely Choreographed Process for Delivering Neurotransmitter into the Synaptic Cleft	166
	The Synaptic Vesicle is the Organelle that Concentrates, Stores, and Delivers Neurotransmitter at the Synapse	167
	Neurotransmitter-Filled Synaptic Vesicles Dock at the Active Zone and Become �Primed� for Exocytosis	167
	Binding of Ca²⁺ Ions to Synaptotagmin Triggers the Fusion and Exocytosis of the Synaptic Vesicle	169
	Retrieval of the Fused Synaptic Vesicle Back into the Nerve Terminal can Occur through Clathrin- Independent and Clathrin- Dependent Mechanisms	171
	Short-Term Synaptic Plasticity is a Transient, Use-Dependent Change in the Efficacy of Synaptic Transmission	174
	Summary	177
	Keywords and Concepts	178
	Study Problems	179
Chapter 13	Synaptic Physiology II	181
	Chemical Synapses Afford Specificity, Variety, and Fine Tuning of Neurotransmission	181
	What is a Neurotransmitter?	181
	Receptors Mediate the Actions of Neurotransmitters in Postsynaptic Cells	184
	Conventional Neurotransmitters Activate Two Classes of Receptors: Ionotropic Receptors and Metabotropic Receptors	184
	Acetylcholine Receptors can be Ionotropic or Metabotropic	186
	Nicotinic Acetylcholine Receptors are Ionotropic	186
	Muscarinic Acetylcholine Receptors are Metabotropic	186
	Amino Acid Neurotransmitters Mediate Many Excitatory and Inhibitory Responses in the Brain	187
	Glutamate is the Main Excitatory Neurotransmitter in the Brain	187
	γ-Aminobutyric Acid and Glycine are the Main Inhibitory Neurotransmitters in the Nervous System	188
	Neurotransmitters that Bind to Ionotropic Receptors Cause Membrane Conductance Changes	189
	At Excitatory Synapses, the Reversal Potential is More Positive Than the Action Potential Threshold	190
	NMDAR and AMPAR are Channels with Different Ion Selectivities and Kinetics	191
	Sustained Application of Agonist Causes Desensitization of Ionotropic Receptors	192
	At Inhibitory Synapses, the Reversal Potential is More Negative Than the Action Potential Threshold	193
	Temporal and Spatial Summation of Postsynaptic Potentials Determine the Outcome of Synoptic Transmission	195
	Synaptk Transmission is Terminated by Several Mechanisms	196
	Biogenic Amines, Purines, and Neuropeptides are Important Classes of Transmitters with a Wide Spectrum of Actions	197
	Epinephrine and Norepinephrine Exert Central and Peripheral Effects by Activating Two Classes of Receptors	197
	Dopaminergic Transmission is Important for the Coordination of Movement and for Cognition	198
	Serotonergic Transmission is Important in Emotion and Behavior	199
	Histamine Serves Diverse Central and Peripheral Functions	200
	ATP is Frequently Coreleased with other Neurotransmitters	200
	Neuropeptide Transmitters are Structurally and Functionally Diverse	201
	Unconventional Neurotransmitters Modulate Many Complex Physiological Responses	202
	Unconventional Neurotransmitters are Secreted in Nonquantal Fashion	202
	Many Effects of Nitric Oxide and Carbon Monoxide are Mediated Locally by Soluble Guanylyl Cyclase	202
	Endocannabinoids can Mediate Retrograde Neurotransmission	202
	Long-Term Synaptic Potentiation and Depression are Persistent Changes in the Efficacy of Synaptic Transmission Induced by Neural Activity	203
	Long-Term Potentiation is a Long- Lasting Increase in the Efficacy of Transmission at Excitatory Synapses	203
	Long-Term Depression is a Long- Lasting Decrease in the Efficacy of Transmission at Excitatory Synapses	205
	Summary	206
	Keywords and Concepts	207
	Study Problems	208
SECTION V	MOLECULAR MOTORS AND MUSCLE CONTRACTION
Chapter 14	Molecular Motors and the Mechanism of Muscle Contraction	211
	Molecular Motors Produce Movement by Converting Chemical Energy Into Kinetic Energy	211
	The Three Types of Molecular Motors are Myosin, Kinesin, and Dynein	211
	Single Skeletal Muscle Fibers are Composed of Many Myofibrils	212
	The Sarcomere is the Basic Unit of Contraction in Skeletal Muscle	212
	Sarcomeres Consist of Interdigitating Thin and Thick Filaments	212
	Thick Filaments are Composed Mostly of Myosin	214
	Thin Filaments in Skeletal Muscle are Composed of Four Major Proteins: Actin, Tropomyosin, Troponin, and Nebulin	214
	Muscle Contraction Results from Thick and Thin Filaments Sliding Past Each Other (The �Sliding Filament� Mechanism)	215
	The Cross-Bridge Cycle Powers Muscle Contraction	216
	In Skeletal and Cardiac Muscles, Ca²⁺ Activates Contraction by Binding to the Regulatory Protein Troponin C	218
	The Structure and Function of Cardiac Muscle and Smooth Muscle are Distinctly Different from those of Skeletal Muscle	220
	Cardiac Muscle is Striated	220
	Cardiac Muscle Cells Require a Continuous Supply of Energy	220
	To Enable the Heart to Act as a Pump, Myocytes Comprising Each Chamber Must Contract Synchronously	220
	Smooth Muscles are Not Striated	220
	In Smooth Muscle, Elevation of Intracellular Ca²⁺ Activates Contraction by Promoting the Phosphorylation of the Myosin Regulatory Light Chain	223
	Summary	226
	Key Words and Concepts	227
	Study Problems	227
Chapter 15	Excitation-Contraction Coupling in Muscle	229
	Skeletal Muscle Contraction is Initiated by a Depolarization of the Surface Membrane	229
	Skeletal Muscle has a High Resting Cl^� Permeability	230
	A Single Action Potential Causes a Brief Contraction Called a Twitch	230
	How Does Depolarization Increase Intracellular Ca²⁺ in Skeletal Muscle?	230
	Direct Mechanical Interaction Between Sarcolemmal and Sarcoplasmic Reticulum Membrane Proteins Mediates Excitation-Contraction Coupling in Skeletal Muscle	231
	In Skeletal Muscle Depolarization of the T-Tubule Membrane is Required for Excitation-Contraction Coupling	231
	In Skeletal Muscle, Extracellular Ca²⁺ is Not Required for Contraction	232
	In Skeletal Muscle, the Sarcoplasmic Reticulum Stores All the Ca²⁺ Needed for Contraction	232
	The Triad is the Structure that Mediates Excitation-Contraction Coupling in Skeletal Muscle	233
	In Skeletal Muscle, Excitation- Contraction Coupling is Mechanical	235
	Skeletal Muscle Relaxes When Ca²⁺ is Returned to the Sarcoplasmic Reticulum by SERCA	235
	Ca²⁺-Induced Ca²⁺ Release is Central to Excitation-Contraction Coupling in Cardiac Muscle	237
	In Cardiac Muscle, Communication Between the Sarcoplasmic Reticulum and Sarcolemma Occurs at Dyads and Peripheral Couplings	237
	Cardiac Excitation-Contraction Coupling Requires Extracellular Ca²⁺ and Ca²⁺ Entry through L-Type Ca²⁺ Channels (Dihydropyridine Receptors)	238
	Ca²⁺ that Enters the Cell During the Cardiac Action Potential Must be Removed to Maintain A Steady State	240
	Cardiac Contraction can be Regulated by Altering Intracellular Ca²⁺	240
	Smooth Muscle Excitation-Contraction Coupling is Fundamentally Different from that in Skeletal and Cardiac Muscles	241
	Smooth Muscles are Highly Diverse	241
	The Density of Innervation Varies Greatly Among Different Types of Smooth Muscles	241
	Some Smooth Muscles are Normally Activated by Depolarization	242
	Some Smooth Muscles can be Activated without Depolarization by Pharmacomechanical Coupling	243
	Ca²⁺ Signaling, Ca²⁺ Sensitivity, and Ca²⁺ Balance in Smooth Muscle may be Altered Under Physiological and Pathophyswlogical Conditions	245
	Summary	246
	Key Words and Concepts	247
	Study Problems	247
Chapter 16	Mechanics of Muscle Contraction	249
	The Total Force Generated by a Skeletal Muscle can be Varied	249
	Whole Muscle Force can be Increased by Recruiting Motor Units	249
	A Single Action Potential Produces a Twitch Contraction	249
	Repetitive Stimulation Produces Fused Contractions	251
	Skeletal Muscle Mechanics is Characterized by Two Fundamental Relationships	252
	The Sliding Filament Mechanism Underlies the Length-Tension Curve	253
	In Isotonic Contractions, Shortening Velocity Decreases as Force Increases	255
	There are Three Types of Skeletal Muscle Motor Units	255
	The Force Generated by Cardiac Muscle is Regulated by Mechanisms that Control Intracellular Ca²⁺	257
	Cardiac Muscle Generates Long- Duration Contractions	257
	Total Force Developed by Cardiac Muscle is Determined by Intracellular Ca²⁺	257
	Mechanical Properties of Cardiac and Skeletal Muscle are Similar But Quantitatively Different	259
	Cardiac and Skeletal Muscles have Similar Length- Tension Relationships	259
	The Contractile Force of the Intact Heart is a Function of Initial (End-Diastolic) Volume	259
	Shortening Velocity is Slower in Cardiac than in Skeletal Muscle	260
	Dynamics of Smooth Muscle Contraction Differ Markedly from those of Skeletal and Cardiac Muscle	260
	Three Key Relationships Characterize Smooth Muscle Function	260
	The Length-Tension Relationship in Smooth Muscles is Consistent with the Sliding Filament Mechanism of Contraction	260
	The Velocity of Shortening is Much Lower in Smooth Muscle Than in Skeletal Muscle	261
	Single Actin-Myosin Molecular Interactions Reveal How Smooth and Skeletal Muscles Generate the Same Amount of Stress Despite Very Different Shortening Velocities	261
	Velocity of Smooth Muscle Shortening and the Amount of Stress Generated Depend on the Extent Ofmyosin Light Chain Phosphorylation	263
	The Kinetic Properties of the Cross- Bridge Cycle Depend on the Myosin Isoforms Expressed in Themyocytes	263
	The Relationships Among Intracellular Ca²⁺, Myosin Light Chain Phosphorylation, and Force in Smooth Muscles is Complex	264
	Tonic Smooth Muscles can Maintain Tension with Little Consumption of ATP	264
	Perspective: Smooth Muscles are Functionally Diverse	265
	Summary	267
	Keywords and Concepts	268
	Study Problems	268
	Epilogue	271
	APPENDIXES
Appendix A	Abbreviations, Symbols, and Numerical Constants	273
	Abbreviations	273
	Symbols	274
	Numerical Constants	274
Appendix B	A Mathematical Refresher	275
	Exponents	275
	Definition of Exponentiation	275
	Multiplication of Exponentials	275
	Meaning of the Number 0 as Exponent	275
	Negative Numbers as Exponents	275
	Division of Exponentials	276
	Exponentials of Exponentials	276
	Fractions as Exponents	276
	Logarithms	276
	Definition of the Logarithm	276
	Logarithm of a Product	277
	Logarithm of an Exponential	277
	Changing the Base of a Logarithm	277
	Solving Quadratic Equations	277
	Differentiation and Derivatives	278
	The Slope of a Graph and the Derivative	278
	Derivative of a Constant Number	279
	Differentiating the Sum or Difference of Functions	279
	Differentiating Composite Functions: the Chain Rule	280
	Derivative of the Natural Logarithm Function	281
	Integration: the Antiderivative and the Definite Integral	281
	Indefinite Integral (Also Known as the Antiderivative)	281
	Definite Integral	282
	Differential Equations	283
	First-Order Equations with Separable Variables	283
	Exponential Decay	283
	First-Order Linear Differential Equations	284
Appendix C	Root-Mean-Squared Displacement of Diffusing Molecules	287
Appendix D	Summary of Elementary Circuit Theory	291
	Cell Membranes are Modeled with Electrical Circuits	291
	Definitions of Electrical Parameters	291
	Electrical Potential and Potential
	Difference	297
	Current	291
	Resistance and Conductance	291
	Capacitance	292
	Current Flow in Simple Circuits	292
	A Battery and Resistor in Parallel	292
	A Resistor and Capacitor in Parallel	294
Appendix E	Answers to Study Problems	299
Appendix F	Review Examination	311
	Answers to Review Examination	323