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Fundamental Physicochemical Concepts | |
Introduction: Homeostasis and Cellular Physiology | p. 1 |
Homeostasis enables the body to survive in diverse environments | p. 1 |
The body is an ensemble of functionally and spatially distinct compartments | p. 2 |
Transport processes are essential to physiological function | p. 4 |
Cellular physiology focuses on membrane-mediated processes and on muscle function | p. 5 |
Summary | p. 5 |
Key words and concepts | p. 6 |
Diffusion and Permeability | p. 7 |
Diffusion is the migration of molecules down a concentration gradient | p. 7 |
Fick's First Law of Diffusion summarizes our intuitive understanding of diffusion | p. 7 |
Essential aspects of diffusion are revealed by quantitive examination of random, microscopic movements of molecules | p. 9 |
Fick's First Law can be used to describe diffusion across a membrane barrier | p. 12 |
Summary | p. 20 |
Key words and concepts | p. 20 |
Study problems | p. 20 |
Osmotic Pressure and Water Movement | p. 21 |
Osmosis is the transport of solvent driven by a difference in solute concentration across a membrane that is impermeable to solute | p. 21 |
Water transport during osmosis leads to changes in volume | p. 22 |
Osmotic pressure drives the net transport of water during osmosis | p. 22 |
Osmotic pressure and hydrostatic pressure are functionally equivalent in their ability to drive water movement through a membrane | p. 25 |
Only impermeant solutes can have permanent osmotic effects | p. 30 |
Summary | p. 32 |
Key words and concepts | p. 35 |
Study problems | p. 35 |
Electrical Consequences of Ionic Gradients | p. 37 |
Ions are typically present at different concentrations on opposite sides of a biomembrane | p. 37 |
Selective ionic permeability through membranes has electrical consequences: the Nernst equation | p. 37 |
The stable resting membrane potential in a living cell is established by balancing multiple ionic fluxes | p. 42 |
The cell can change its membrane potential by selectively changing membrane permeability to certain ions | p. 48 |
The Donnan effect is an osmotic threat to living cells | p. 48 |
Summary | p. 49 |
Key words and concepts | p. 52 |
Study problems | p. 52 |
Ion Channels and Excitable Membranes | |
Ion Channels | p. 53 |
Ion channels are critical determinants of the electrical behavior of membranes | p. 53 |
Distinct types of ion channels have several common properties | p. 54 |
Ion channels share structural similarities and can be grouped into gene families | p. 56 |
Summary | p. 59 |
Key words and concepts | p. 61 |
Study problems | p. 61 |
Passive Electrical Properties of Membranes | p. 63 |
The time course and spread of membrane potential changes are predicted by the passive electrical properties of the membrane | p. 63 |
The equivalent circuit of an excitable membrane has a resistor in parallel with a capacitor | p. 64 |
Passive membrane properties produce linear current-voltage relationships | p. 65 |
Membrane capacitance affects the time course of voltage changes | p. 65 |
Membrane and axoplasmic resistances affect the passive spread of subthreshold electrical signals | p. 69 |
Summary | p. 73 |
Key words and concepts | p. 73 |
Study problems | p. 74 |
Generation and Propagation of the Action Potential | p. 75 |
The action potential is a rapid and transient depolarization of the membrane potential in electrically excitable cells | p. 75 |
Ion channel function is studied with a voltage clamp | p. 77 |
Individual ion channels have two conductance levels | p. 83 |
Sodium channels inactivate during maintained depolarization | p. 84 |
The action potential is generated by voltage-gated Na[superscript +] and K[superscript +] channels | p. 86 |
Action potential propagation occurs as a result of local circuit currents | p. 89 |
Summary | p. 96 |
Key words and concepts | p. 96 |
Study problems | p. 97 |
Ion Channel Diversity | p. 99 |
Various types of ion channels help to regulate cellular processes | p. 99 |
Voltage-gated Ca[superscript 2+] channels contribute to electrical activity and mediate Ca[superscript 2+] entry into cells | p. 99 |
Potassium-selective channels are the most diverse type of channel | p. 104 |
Ligand-gated channels are gated by agonist binding | p. 111 |
Ion channel activity can be regulated by second-messenger pathways | p. 113 |
Summary | p. 115 |
Key words and concepts | p. 115 |
Study problems | p. 116 |
Solute Transport | |
Electrochemical Potential Energy and Transport Processes | p. 117 |
Electrochemical potential energy drives all transport processes | p. 117 |
Summary | p. 126 |
Key words and concepts | p. 126 |
Study problems | p. 126 |
Passive Solute Transport | p. 127 |
Diffusion across biological membranes is limited by lipid solubility | p. 127 |
Channel, carrier, and pump proteins mediate transport across biological membranes | p. 128 |
Carriers are integral membrane proteins that open to only one side of the membrane at a time | p. 130 |
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 | p. 134 |
Sodium is cotransported with a variety of solutes such as glucose and amino acids | p. 136 |
Net transport of some solutes across epithelia is effected by coupling two transport processes in series | p. 139 |
Sodium is exchanged for solutes such as calcium and protons by countertransport mechanisms | p. 141 |
Multiple transport systems can be functionally coupled | p. 144 |
Summary | p. 146 |
Key words and concepts | p. 147 |
Study problems | p. 147 |
Active Transport | p. 149 |
Primary active transport converts the chemical energy from ATP into electrochemical potential energy stored in solute gradients | p. 149 |
The plasma membrane Na[superscript +] pump (Na, K-ATPase) maintains the low Na[superscript +] and high K[superscript +] concentrations in the cytosol | p. 150 |
Intracellular Ca[superscript 2+] signaling is universal and is closely tied to Ca[superscript 2+] homeostasis | p. 154 |
Ca[superscript 2+] storage in the sarcoplasmic/endoplasmic reticulum is mediated by a Ca[superscript 2+]-ATPase | p. 157 |
The plasma membrane of most cells also has an ATP-driven Ca[superscript 2+] pump | p. 158 |
Transport systems may be functionally coupled in parallel or in series | p. 160 |
Several other plasma membrane transport ATPases also play important physiological roles | p. 160 |
Net transport across epithelial cells depends on the coupling of apical and basolateral membrane transport systems | p. 165 |
Summary | p. 174 |
Key words and concepts | p. 175 |
Study problems | p. 175 |
Molecular Motors and Muscle Contraction | |
Molecular Motors and the Mechanisms of Muscle Contraction | p. 177 |
Molecular motors produce motility by converting chemical energy into kinetic energy | p. 177 |
Single skeletal muscle fibers are composed of many myofibrils | p. 178 |
The sarcomere is the basic unit of contraction in skeletal muscle | p. 178 |
According to the "sliding filament" mechanism, muscle contraction results from thin and thick filaments sliding past each other | p. 182 |
The cross-bridge cycle powers muscle contraction | p. 184 |
In skeletal and cardiac muscles, Ca[superscript 2+] activates contraction by binding to the regulatory protein troponin C | p. 188 |
The structure and function of cardiac muscle and smooth muscle-are distinctly different from those of skeletal muscle | p. 188 |
Summary | p. 196 |
Key words and concepts | p. 196 |
Study problems | p. 197 |
Excitation-Contraction Coupling in Muscle | p. 199 |
Skeletal muscle contraction is initiated by a depolarization of the surface membrane | p. 199 |
Direct mechanical interaction between sarcolemmal and sarcoplasmic reticulum membrane proteins may mediate excitation-contraction coupling in skeletal muscle | p. 202 |
Ca[superscript 2+]-induced Ca[superscript 2+] release is central to excitation-contraction coupling in cardiac muscle | p. 208 |
Activation of smooth muscle differs in fundamental ways from excitation-contraction coupling in skeletal and cardiac muscles | p. 211 |
Summary | p. 221 |
Key words and concepts | p. 222 |
Study problems | p. 222 |
Mechanics of Muscle Contraction | p. 225 |
The total force generated by a skeletal muscle can be varied by several mechanisms | p. 225 |
Skeletal muscle mechanics is characterized by two fundamental relationships | p. 229 |
There are three main types of phasic skeletal muscle motor units | p. 232 |
The force generated by cardiac muscle is regulated by various mechanisms that control [Ca superscript 2+ subscript i] | p. 234 |
The mechanical properties of cardiac and skeletal muscle are similar, but there are significant quantitative differences | p. 235 |
The dynamic properties of smooth muscle contraction differ markedly from those of skeletal and cardiac muscle | p. 238 |
Some properties of specific types of smooth muscles can be resolved by a study of individual myosin motors | p. 241 |
The relationship among [Ca superscript 2+ subscript i] concentration, myosin phosphorylation, and mechanical force in smooth muscles is complex | p. 242 |
Summary | p. 246 |
Key words and concepts | p. 249 |
Study problems | p. 249 |
Epilogue | p. 251 |
Appendixes | |
A Mathematical Refresher | p. 255 |
Exponents | p. 255 |
Logarithms | p. 257 |
Solving quadratic equations | p. 258 |
Differentiation and derivatives | p. 258 |
Integration: the antiderivative and the definite integral | p. 263 |
Differential equations | p. 264 |
Root-Mean-Squared Displacement of Diffusing Molecules | p. 267 |
Summary of Elementary Circuit Theory | p. 271 |
Cell membranes are modeled with electrical circuits | p. 271 |
Definitions of electrical parameters | p. 271 |
Current flow in simple circuits | p. 273 |
Answers to Study Problems | p. 281 |
Review Examination | p. 295 |
Answers to review examination | p. 309 |
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