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Cellular Physiology and Neurophysiology E-Book

Cellular Physiology and Neurophysiology E-Book

Mordecai P. Blaustein | Joseph P. Y. Kao | Donald R. Matteson



Gain a quick and easy understanding of this complex subject with the 2nd edition of Cellular Physiology and Neurophysiology by doctors Mordecai P. Blaustein, Joseph PY Kao, and Donald R. Matteson. The expanded and thoroughly updated content in this Mosby Physiology Monograph Series title bridges the gap between basic biochemistry, molecular and cell biology, neuroscience, and organ and systems physiology, providing the rich, clinically oriented coverage you need to master the latest concepts in neuroscience. See how cells function in health and disease with extensive discussion of cell membranes, action potentials, membrane proteins/transporters, osmosis, and more. Intuitive and user-friendly, this title is a highly effective way to learn cellular physiology and neurophysiology. 

  • Focus on the clinical implications of the material with frequent examples from systems physiology, pharmacology, and pathophysiology.
  • Gain a solid grasp of transport processes—which are integral to all physiological processes, yet are neglected in many other cell biology texts.
  • Understand therapeutic interventions and get an updated grasp of the field with information on recently discovered molecular mechanisms.
  • Conveniently explore mathematical derivations with special boxes throughout the text.

Test your knowledge of the material with an appendix of multiple-choice review questions, complete with correct answers

  • Understand the latest concepts in neurophysiology with a completely new section on Synaptic Physiology.
  • Learn all of the newest cellular physiology knowledge with sweeping updates throughout.
  • Reference key abbreviations, symbols, and numerical constants at a glance with new appendices.

Table of Contents

Section Title Page Action Price
Front cover Cover
Cellular physiology and neurophysiology iii
Copyright iv
Preface v
Acknowledgments vii
Table of contents ix
I Fundamental physicochemical concepts 1
Introduction: homeostasis and cellular physiology 1
Objectives 1
Key words and concepts 5
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 organelles 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
Bibliography 5
Diffusion and permeability 7
Objectives 7
Key words and concepts 18
Diffusion is 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
Study problems 18
Bibliography 18
Osmotic pressure and water movement 19
Objectives 19
Key words and concepts 32
Osmosis is the transport of solvent driven by a difference in solute concentration across a membrane that is impermeable t ... 19
Water transport during osmosis leads to changes in volume 20
Osmotic pressure drives the net transport of water during osmosis 20
Osmotic pressure and hydrostatic pressure are functionally equivalent in their ability to drive water movement through a m ... 22
The direction of fluid flow through the capillary wall is determined by the balance of hydrostatic and osmotic pressures, ... 23
Only impermeant solutes can have permanent osmotic effects 27
Transient changes in cell volume occur in response to changes in the extracellular concentration of permeant 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
Study problems 32
Bibliography 32
Electrical consequences of ionic gradients 33
Objectives 33
Key words and concepts 46
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
Ek is the “floor” and ena 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
Study problems 46
Bibliography 46
II Ion Channels and Excitable Membranes 47
Ion channels 47
Objectives 47
Key words and concepts 54
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
Study problems 54
Bibliography 54
Passive electrical properties of membranes 55
Objectives 55
Key words and concepts 64
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
Study problems 64
Bibliography 65
Generation and propagation of the action potential 67
Objectives 67
Key words and concepts 84
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 a ... 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
Study problems 84
Bibliography 85
Ion channel diversity 87
Objectives 87
Key words and concepts 100
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 β-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
β-adrenergic receptor activation modulates l-type ca2+ channels in cardiac muscle 99
Summary 99
Study problems 100
Bibliography 101
III Solute transport 103
Electrochemical potential energy and transport processes 103
Objectives 103
Key words and concepts 111
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
Study problems 111
Bibliography 111
Passive solute transport 113
Objectives 113
Key words and concepts 130
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 ŁŁgatingŁŁ 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 ŁŁdownhillŁŁ transport of another solute enables carriers to move the ... 119
Na+/h+ exchange is an example of na+-coupled countertransport 119
Na+ is cotransported with a variety of solutes such as glucose and amino acids 119
How does the electrochemical gradient for one solute affect the gradient for a cotransported solute? 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
Study problems 131
Bibliography 131
Active transport 133
Objectives 133
Key words and concepts 148
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 and digoxin 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 also 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
Study problems 154
Bibliography 154
IV Physiology of synaptic transmission 155
Synaptic physiology i 155
Objectives 155
Key words and concepts 178
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+ plays 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+ 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-d ... 171
Short-term synaptic plasticity is a transient, use-dependent change in the efficacy of synaptic transmission 174
Summary 177
Study problems 179
Bibliography 179
Synaptic physiology ii 181
Objectives 181
Key words and concepts 207
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 synaptic transmission 195
Synaptic 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 ... 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
Study problems 208
Bibliography 209
V Molecular motors and muscle contraction 211
Molecular motors and the mechanism of muscle contraction 211
Objectives 211
Key words and concepts 227
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 reg ... 223
Summary 226
Study problems 227
Bibliography 227
Excitation-contraction coupling in muscle 229
Objectives 229
Key words and concepts 247
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-contrac ... 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 (dihydropy ... 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 pathophysiologi ... 245
Summary 246
Study problems 247
Bibliography 247
Mechanics of muscle contraction 249
Objectives 249
Key words and concepts 268
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 despi ... 261
Velocity of smooth muscle shortening and the amount of stress generated depend on the extent of myosin light chain phospho ... 263
The kinetic properties of the cross-bridge cycle depend on the myosin isoforms expressed in the myocytes 263
The relationships among intracelllular 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
Study problems 268
Bibliography 269
Epilogue 271
Bibliography 272
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
An example illustrating the computation of a derivative 280
What makes the “natural” exponential function natural? 280
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
Root-mean-squared displacement of diffusing molecules 287
Bibliography 289
Summary of elementary circuit theory 291
Cell membranes are modeled with electrical circuits 291
Definitions of electrical parameters 291
Electrical potential and potential difference 291
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
Answers to study problems 299
Chapter 2 299
Chapter 3 299
Chapter 4 300
Chapter 5 301
Chapter 6 301
Chapter 7 302
Chapter 8 303
Chapter 9 304
Chapter 10 304
Chapter 11 305
Chapter 12 306
Chapter 13 306
Chapter 14 307
Chapter 15 308
Chapter 16 308
Review examination 311
Answers to review examination 323
Index 325
A 325
B 326
C 326
D 328
E 328
F 329
G 330
H 330
I 330
J 331
K 331
L 331
M 331
N 332
O 333
P 333
Q 334
R 334
S 335
T 336
U 337
V 337
W 337
X 337
Z 337