Medical Physiology

Medical Physiology Copyright Page Contributors Video Table of Contents Preface to the Third Edition The eBook Acknowledgments Preface to the First Edition Target Audience Content of the Textbook Emphasis of the Textbook Creating the Textbook Special Features Acknowledgments Chapter 1 1 Foundations of Physiology What is physiology? Physiological genomics is the link between the organ and the gene Cells live in a highly protected milieu intérieur Homeostatic mechanisms—operating through sophisticated feedback control mechanisms— are responsible for maintaining the constancy of the milieu intérieur Medicine is the study of “physiology gone awry” References References Chapter 2 2 Functional Organization of the Cell Structure of Biological Membranes The surface of the cell is defined by a membrane The cell membrane is composed primarily of phospholipids Phospholipids form complex structures in aqueous solution The diffusion of individual lipids within a leaflet of a bilayer is determined by the chemical makeup of its constituents Phospholipid bilayer membranes are impermeable to charged molecules The plasma membrane is a bilayer Membrane proteins can be integrally or peripherally associated with the plasma membrane The membrane-spanning portions of transmembrane proteins are usually hydrophobic α helices Some membrane proteins are mobile in the plane of the bilayer Function of Membrane Proteins Integral membrane proteins can serve as receptors Integral membrane proteins can serve as adhesion molecules Integral membrane proteins can carry out the transmembrane movement of water-soluble substances Integral membrane proteins can also be enzymes Integral membrane proteins can participate in intracellular signaling Peripheral membrane proteins participate in intracellular signaling and can form a submembranous cytoskeleton Cellular Organelles and the Cytoskeleton The cell is composed of discrete organelles that subserve distinct functions The nucleus stores, replicates, and reads the cell’s genetic information Lysosomes digest material derived from the interior and exterior of the cell The mitochondrion is the site of oxidative energy production The cytoplasm is not amorphous but is organized by the cytoskeleton Intermediate filaments provide cells with structural support Microtubules provide structural support and provide the basis for several types of subcellular motility Thin filaments (actin) and thick filaments (myosin) are present in almost every cell type Synthesis and Recycling of Membrane Proteins Secretory and membrane proteins are synthesized in association with the rough ER Simultaneous protein synthesis and translocation through the rough ER membrane requires machinery for signal recognition and protein translocation Proper insertion of membrane proteins requires start- and stop-transfer sequences Newly synthesized secretory and membrane proteins undergo post-translational modification and folding in the lumen of the rough ER Secretory and membrane proteins follow the secretory pathway through the cell Carrier vesicles control the traffic between the organelles of the secretory pathway Specialized protein complexes, such as clathrin and coatamers, mediate the formation and fusion of vesicles in the secretory pathway Vesicle Formation in the Secretory Pathway Vesicle Fusion in the Secretory Pathway Newly synthesized secretory and membrane proteins are processed during their passage through the secretory pathway Newly synthesized proteins are sorted in the trans-Golgi network A mannose-6-phosphate recognition marker is required to target newly synthesized hydrolytic enzymes to lysosomes Cells internalize extracellular material and plasma membrane through the process of endocytosis Receptor-mediated endocytosis is responsible for internalizing specific proteins Endocytosed proteins can be targeted to lysosomes or recycled to the cell surface Certain molecules are internalized through an alternative process that involves caveolae Specialized Cell Types Epithelial cells form a barrier between the internal and external milieu Tight Junctions Adhering Junctions Gap Junctions Desmosomes Epithelial cells are polarized References References Books and Reviews Journal Articles Chapter 3 3 Signal Transduction Mechanisms of Cellular Communication Cells can communicate with one another via chemical signals Soluble chemical signals interact with target cells via binding to surface or intracellular receptors Cells can also communicate by direct interactions—juxtacrine signaling Gap Junctions Adhering and Tight Junctions Membrane-Associated Ligands Ligands in the Extracellular Matrix Second-messenger systems amplify signals and integrate responses among cell types Receptors That are Ion Channels Ligand-gated ion channels transduce a chemical signal into an electrical signal Receptors Coupled to G Proteins General Properties of G Proteins G proteins are heterotrimers that exist in many combinations of different α, β, and γ subunits G-protein activation follows a cycle Activated α subunits couple to a variety of downstream effectors, including enzymes and ion channels βγ subunits can activate downstream effectors Small GTP-binding proteins are involved in a vast number of cellular processes G-Protein Second Messengers: Cyclic Nucleotides cAMP usually exerts its effect by increasing the activity of protein kinase A Protein phosphatases reverse the action of kinases cGMP exerts its effect by stimulating a nonselective cation channel in the retina G-Protein Second Messengers: Products of Phosphoinositide Breakdown Many messengers bind to receptors that activate phosphoinositide breakdown IP3 liberates Ca2+ from intracellular stores Calcium activates calmodulin-dependent protein kinases DAGs and Ca2+ activate protein kinase C G-Protein Second Messengers: Arachidonic Acid Metabolites Phospholipase A2 is the primary enzyme responsible for releasing AA Cyclooxygenases, lipoxygenases, and epoxygenases mediate the formation of biologically active eicosanoids Prostaglandins, prostacyclins, and thromboxanes (cyclooxygenase products) are vasoactive, regulate platelet action, and modulate ion transport N3-16 The leukotrienes (5-lipoxygenase products) play a major role in inflammatory responses The HETEs and EETs (epoxygenase products) tend to enhance Ca2+ release from intracellular stores and to enhance cell proliferation Degradation of the eicosanoids terminates their activity Receptors That are Catalytic The receptor guanylyl cyclase transduces the activity of atrial natriuretic peptide, whereas a soluble guanylyl cyclase transduces the activity of nitric oxide Receptor (Membrane-Bound) Guanylyl Cyclase Soluble Guanylyl Cyclase Some catalytic receptors are serine/threonine kinases RTKs produce phosphotyrosine motifs recognized by SH2 and phosphotyrosine-binding domains of downstream effectors Creation of Phosphotyrosine Motifs Recognition of pY Motifs by SH2 and Phosphotyrosine-Binding Domains The MAPK Pathway The Phosphatidylinositol-3-Kinase Pathway Tyrosine kinase–associated receptors activate cytosolic tyrosine kinases such as Src and JAK Receptor tyrosine phosphatases are required for lymphocyte activation Nuclear Receptors Steroid and thyroid hormones enter the cell and bind to members of the nuclear receptor superfamily in the cytoplasm or nucleus Activated nuclear receptors bind to sequence elements in the regulatory region of responsive genes and either activate or repress DNA transcription References References Books and Reviews Journal Articles Chapter 4 4 Regulation of Gene Expression From Genes to Proteins Gene expression differs among tissues and—in any tissue—may vary in response to external stimuli Genetic information flows from DNA to proteins The gene consists of a transcription unit DNA is packaged into chromatin Gene expression may be regulated at multiple steps Transcription factors are proteins that regulate gene transcription The Promoter and Regulatory Elements The basal transcriptional machinery mediates gene transcription The promoter determines the initiation site and direction of transcription Positive and negative regulatory elements modulate gene transcription Locus control regions and insulator elements influence transcription within multigene chromosomal domains Transcription Factors DNA-binding transcription factors recognize specific DNA sequences Transcription factors that bind to DNA can be grouped into families based on tertiary structure Zinc Finger Basic Zipper Basic Helix-Loop-Helix Helix-Turn-Helix Coactivators and corepressors are transcription factors that do not bind to DNA Transcriptional activators stimulate transcription by three mechanisms Recruitment of the Basal Transcriptional Machinery Chromatin Remodeling Stimulation of Pol II Transcriptional activators act in combination Transcriptional repressors act by competition, quenching, or active repression The activity of transcription factors may be regulated by post-translational modifications Phosphorylation Site-Specific Proteolysis Other Post-Translational Modifications The expression of some transcription factors is tissue specific Regulation of Inducible Gene Expression by Signal-Transduction Pathways cAMP regulates transcription via the transcription factors CREB and CBP Receptor tyrosine kinases regulate transcription via a Ras-dependent cascade of protein kinases Tyrosine kinase–associated receptors can regulate transcription via JAK-STAT Nuclear receptors are transcription factors Modular Construction Dimerization Activation of Transcription Repression of Transcription Physiological stimuli can modulate transcription factors, which can coordinate complex cellular responses Epigenetic Regulation of Gene Expression Epigenetic regulation can result in long-term gene silencing Alterations in chromatin structure may mediate epigenetic regulation, stimulating or inhibiting gene transcription Histone methylation may stimulate or inhibit gene expression DNA methylation is associated with gene inactivation Post-Translational Regulation of Gene Expression Alternative splicing generates diversity from single genes Retained Intron Alternative 3′ Splice Sites Alternative 5′ Splice Sites Cassette Exons Mutually Exclusive Exons Alternative 5′ Ends Alternative 3′ Ends Regulatory elements in the 3′ untranslated region control mRNA stability MicroRNAs regulate mRNA abundance and translation References References Books and Reviews Journal Articles Glossary Chapter 5 5 Transport of Solutes and Water The Intracellular and Extracellular Fluids Total-body water is the sum of the ICF and ECF volumes Plasma Volume Interstitial Fluid Transcellular Fluid ICF is rich in K+, whereas ECF is rich in Na+ and Cl− Volume Occupied by Plasma Proteins Effect of Protein Charge All body fluids have approximately the same osmolality, and each fluid has equal numbers of positive and negative charges Osmolality Electroneutrality Solute Transport Across Cell Membranes In passive, noncoupled transport across a permeable membrane, a solute moves down its electrochemical gradient At equilibrium, the chemical and electrical potential energy differences across the membrane are equal but opposite (Vm − EX) is the net electrochemical driving force acting on an ion In simple diffusion, the flux of an uncharged substance through membrane lipid is directly proportional to its concentration difference Some substances cross the membrane passively through intrinsic membrane proteins that can form pores, channels, or carriers Water-filled pores can allow molecules, some as large as 45 kDa, to cross membranes passively Gated channels, which alternately open and close, allow ions to cross the membrane passively Na+ Channels K+ Channels Ca2+ Channels Proton Channels Anion Channels Some carriers facilitate the passive diffusion of small solutes such as glucose The physical structures of pores, channels, and carriers are quite similar The Na-K pump, the most important primary active transporter in animal cells, uses the energy of ATP to extrude Na+ and take up K+ Besides the Na-K pump, other P-type ATPases include the H-K and Ca pumps H-K Pump Ca Pumps Other Pumps The F-type and the V-type ATPases transport H+ F-type or FoF1 ATPases V-type H Pump ATP-binding cassette transporters can act as pumps, channels, or regulators ABCA Subfamily MDR Subfamily MRP/CFTR Subfamily Cotransporters, one class of secondary active transporters, are generally driven by the energy of the inwardly directed Na+ gradient Na/Glucose Cotransporter Na+-Driven Cotransporters for Organic Solutes Na/HCO3 Cotransporters Na+-Driven Cotransporters for Other Inorganic Anions Na/K/Cl Cotransporter Na/Cl Cotransporter K/Cl Cotransporter H+-Driven Cotransporters Exchangers, another class of secondary active transporters, exchange ions for one another Na-Ca Exchanger Na-H Exchanger Na+-Driven Cl-HCO3 Exchanger Cl-HCO3 Exchanger Other Anion Exchangers Regulation of Intracellular Ion Concentrations The Na-K pump keeps [Na+] inside the cell low and [K+] high The Ca pump and the Na-Ca exchanger keep intracellular [Ca2+] four orders of magnitude lower than extracellular [Ca2+] Ca Pump (SERCA) in Organelle Membranes Ca Pump (PMCA) on the Plasma Membrane Na-Ca Exchanger (NCX) on the Plasma Membrane In most cells, [Cl−] is modestly above equilibrium because Cl− uptake by the Cl-HCO3 exchanger and Na/K/Cl cotransporter balances passive Cl− efflux through channels The Na-H exchanger and Na+-driven transporters keep the intracellular pH and [] above their equilibrium values Water Transport and the Regulation of Cell Volume Water transport is driven by osmotic and hydrostatic pressure differences across membranes Because of the presence of impermeant, negatively charged proteins within the cell, Donnan forces will lead to cell swelling The Na-K pump maintains cell volume by doing osmotic work that counteracts the passive Donnan forces Cell volume changes trigger rapid changes in ion channels or transporters, returning volume toward normal Response to Cell Shrinkage Response to Cell Swelling Cells respond to long-term hyperosmolality by accumulating new intracellular organic solutes The gradient in tonicity—or effective osmolality—determines the osmotic flow of water across a cell membrane Water Exchange Across Cell Membranes Water Exchange Across the Capillary Wall Adding isotonic saline, pure water, or pure NaCl to the ECF will increase ECF volume but will have divergent effects on ICF volume and ECF osmolality Infusion of Isotonic Saline Infusion of “Solute-Free” Water Ingestion of Pure NaCl Salt Whole-body Na+ content determines ECF volume, whereas whole-body water content determines osmolality Transport of Solutes and Water Across Epithelia The epithelial cell generally has different electrochemical gradients across its apical and basolateral membranes Tight and leaky epithelia differ in the permeabilities of their tight junctions Epithelial cells can absorb or secrete different solutes by inserting specific channels or transporters at either the apical or basolateral membrane Na+ Absorption K+ Secretion Glucose Absorption Cl− Secretion Water transport across epithelia passively follows solute transport Absorption of a Hyperosmotic Fluid Absorption of an Isosmotic Fluid Absorption of a Hypo-osmotic Fluid Epithelia can regulate transport by controlling transport proteins, tight junctions, and the supply of the transported substances Increased Synthesis (or Degradation) of Transport Proteins Recruitment of Transport Proteins to the Cell Membrane Post-translational Modification of Pre-existing Transport Proteins Changes in the Paracellular Pathway Luminal Supply of Transported Species and Flow Rate References References Books and Reviews Journal Articles Chapter 6 6 Electrophysiology of the Cell Membrane Ionic Basis of Membrane Potentials Principles of electrostatics explain why aqueous pores formed by channel proteins are needed for ion diffusion across cell membranes Membrane potentials can be measured with microelectrodes as well as dyes or fluorescent proteins that are voltage sensitive Membrane potential is generated by ion gradients For mammalian cells, Nernst potentials for ions typically range from −100 mV for K+ to +100 mV for Ca2+ Currents carried by ions across membranes depend on the concentration of ions on both sides of the membrane, the membrane potential, and the permeability of the membrane to each ion Membrane potential depends on ionic concentration gradients and permeabilities Electrical Model of a Cell Membrane The cell membrane model includes various ionic conductances and electromotive forces in parallel with a capacitor The separation of relatively few charges across the bilayer capacitance maintains the membrane potential Ionic current is directly proportional to the electrochemical driving force (Ohm’s law) Capacitative current is proportional to the rate of voltage change A voltage clamp measures currents across cell membranes The patch-clamp technique resolves unitary currents through single channel molecules Single channel currents sum to produce macroscopic membrane currents Single channels can fluctuate between open and closed states Molecular Physiology of Ion Channels Classes of ion channels can be distinguished on the basis of electrophysiology, pharmacological and physiological ligands, intracellular messengers, and sequence homology Electrophysiology Pharmacological Ligands Physiological Ligands Intracellular Messengers Sequence Homology Many channels are formed by a radially symmetric arrangement of subunits or domains around a central pore Gap junction channels are made up of two connexons, each of which has six identical subunits called connexins An evolutionary tree called a dendrogram illustrates the relatedness of ion channels Hydrophobic domains of channel proteins can predict how these proteins weave through the membrane Protein superfamilies, subfamilies, and subtypes are the structural bases of channel diversity Connexins K+ Channels HCN, CNG, and TRP Channels NAADP Receptor Voltage-Gated Na+ Channels Voltage-Gated Ca2+ Channels CatSper Channels Hv Channels Ligand-Gated Channels Other Ion Channels References References Books and Reviews Journal Articles Chapter 7 7 Electrical Excitability and Action Potentials Mechanisms of Nerve and Muscle Action Potentials An action potential is a transient depolarization triggered by a depolarization beyond a threshold In contrast to an action potential, a graded response is proportional to stimulus intensity and decays with distance along the axon Excitation of a nerve or muscle depends on the product (strength × duration) of the stimulus and on the refractory period The action potential arises from changes in membrane conductance to Na+ and K+ The Na+ and K+ currents that flow during the action potential are time and voltage dependent Time Dependence of Na+ and K+ Currents Voltage Dependence of Na+ and K+ Currents Macroscopic Na+ and K+ currents result from the opening and closing of many channels The Hodgkin-Huxley model predicts macroscopic currents and the shape of the action potential Physiology of Voltage-Gated Channels and Their Relatives A large superfamily of structurally related membrane proteins includes voltage-gated and related channels Na+ channels generate the rapid initial depolarization of the action potential Na+ channels are blocked by neurotoxins and local anesthetics Ca2+ channels contribute to action potentials in some cells and also function in electrical and chemical coupling mechanisms Ca2+ channels are characterized as L-, T-, P/Q-, N-, and R-type channels on the basis of kinetic properties and inhibitor sensitivity K+ channels determine resting potential and regulate the frequency and termination of action potentials The Kv (or Shaker-related) family of K+ channels mediates both the delayed outward-rectifier current and the transient A-type current Two families of KCa K+ channels mediate Ca2+-activated K+ currents The Kir K+ channels mediate inward-rectifier K+ currents, and K2P channels may sense stress Propagation of Action Potentials The propagation of electrical signals in the nervous system involves local current loops Myelin improves the efficiency with which axons conduct action potentials The cable properties of the membrane and cytoplasm determine the velocity of signal propagation References References Books and Reviews Journal Articles Chapter 8 8 Synaptic Transmission and the Neuromuscular Junction Mechanisms of Synaptic Transmission Electrical continuity between cells is established by electrical or chemical synapses Electrical synapses directly link the cytoplasm of adjacent cells Chemical synapses use neurotransmitters to provide electrical continuity between adjacent cells Neurotransmitters can activate ionotropic or metabotropic receptors Synaptic Transmission at the Neuromuscular Junction Neuromuscular junctions are specialized synapses between motor neurons and skeletal muscle ACh activates nicotinic AChRs to produce an excitatory end-plate current The nicotinic AChR is a member of the pentameric Cys-loop receptor family of ligand-gated ion channels Activation of AChR channels requires binding of two ACh molecules Miniature EPPs reveal the quantal nature of transmitter release from the presynaptic terminals Direct sensing of extracellular transmitter also shows quantal release of transmitter Synaptic vesicles package, store, and deliver neurotransmitters Neurotransmitter release occurs by exocytosis of synaptic vesicles Re-uptake or cleavage of the neurotransmitter terminates its action Toxins and Drugs Affecting Synaptic Transmission Guanidinium neurotoxins such as tetrodotoxin prevent depolarization of the nerve terminal, whereas dendrotoxins inhibit repolarization ω-Conotoxin blocks Ca2+ channels that mediate Ca2+ influx into nerve terminals, inhibiting synaptic transmission Bacterial toxins such as tetanus and botulinum toxins cleave proteins involved in exocytosis, preventing fusion of synaptic vesicles Both agonists and antagonists of the nicotinic AChR can prevent synaptic transmission Inhibitors of AChE prolong and magnify the EPP References References Books and Reviews Journal Articles Chapter 9 9 Cellular Physiology of Skeletal, Cardiac, and Smooth Muscle Skeletal Muscle Contraction of skeletal muscle is initiated by motor neurons that innervate motor units Action potentials propagate from the sarcolemma to the interior of muscle fibers along the transverse tubule network Depolarization of the T-tubule membrane results in Ca2+ release from the SR at the triad Striations of skeletal muscle fibers correspond to ordered arrays of thick and thin filaments within myofibrils Thin and thick filaments are supramolecular assemblies of protein subunits Thin Filaments Thick Filaments During the cross-bridge cycle, contractile proteins convert the energy of ATP hydrolysis into mechanical energy An increase in [Ca2+]i triggers contraction by removing the inhibition of cross-bridge cycling Termination of contraction requires re-uptake of Ca2+ into the SR Muscle contractions produce force under isometric conditions and force with shortening under isotonic conditions Muscle length influences tension development by determining the degree of overlap between actin and myosin filaments At higher loads, the velocity of shortening is lower because more cross-bridges are simultaneously active In a single skeletal muscle fiber, the force developed may be increased by summing multiple twitches in time In a whole skeletal muscle, the force developed may be increased by summing the contractions of multiple fibers Cardiac Muscle Action potentials propagate between adjacent cardiac myocytes through gap junctions Cardiac contraction requires Ca2+ entry through L-type Ca2+ channels Cross-bridge cycling and termination of cardiac muscle contraction are similar to the events in skeletal muscle In cardiac muscle, increasing the entry of Ca2+ enhances the contractile force Smooth Muscle Smooth muscles may contract in response to synaptic transmission or electrical coupling Action potentials of smooth muscles may be brief or prolonged Some smooth-muscle cells spontaneously generate either pacemaker currents or slow waves Some smooth muscles contract without action potentials In smooth muscle, both entry of extracellular Ca2+ and intracellular Ca2+ spark activate contraction Ca2+ Entry via Voltage-Gated Channels Ca2+ Release from the SR Ca2+ Entry through Store-Operated Ca2+ Channels (SOCs) Ca2+-dependent phosphorylation of the myosin regulatory light chain activates cross-bridge cycling in smooth muscle Termination of smooth-muscle contraction requires dephosphorylation of myosin light chain Smooth-muscle contraction may also occur independently of increases in [Ca2+]i In smooth muscle, increases in both [Ca2+]i and the Ca2+ sensitivity of the contractile apparatus enhance contractile force Smooth muscle maintains high force at low energy consumption Diversity among Muscles Skeletal muscle is composed of slow-twitch and fast-twitch fibers The properties of cardiac cells vary with location in the heart The properties of smooth-muscle cells differ markedly among tissues and may adapt with time Smooth-muscle cells express a wide variety of neurotransmitter and hormone receptors References References Books and Reviews Journal Articles Chapter 10 10 Organization of the Nervous System The nervous system can be divided into central, peripheral, and autonomic nervous systems Each area of the nervous system has unique nerve cells and a different function Cells of the Nervous System The neuron doctrine first asserted that the nervous system is composed of many individual signaling units—the neurons Nerve cells have four specialized regions: cell body, dendrites, axon, and presynaptic terminals Cell Body Dendrites Axon Presynaptic Terminals The cytoskeleton helps compartmentalize the neuron and also provides the tracks along which material travels between different parts of the neuron Fast Axoplasmic Transport Fast Retrograde Transport Slow Axoplasmic Transport Neurons can be classified on the basis of their axonal projection, their dendritic geometry, and the number of processes emanating from the cell body Axonal Projection Dendritic Geometry Number of Processes Glial cells provide a physiological environment for neurons Development of Neurons and Glial Cells Neurons differentiate from the neuroectoderm Neurons and glial cells originate from cells in the proliferating germinal matrix near the ventricles Neurons migrate to their correct anatomical position in the brain with the help of adhesion molecules Neurons do not regenerate Neurons Axons Glia Subdivisions of the Nervous System The CNS consists of the telencephalon, cerebellum, diencephalon, midbrain, pons, medulla, and spinal cord Telencephalon Cerebellum Diencephalon Brainstem (Midbrain, Pons, and Medulla) Spinal Cord The PNS comprises the cranial and spinal nerves, their associated sensory ganglia, and various sensory receptors The ANS innervates effectors that are not under voluntary control References References Books and Reviews Journal Articles Chapter 11 11 The Neuronal Microenvironment Extracellular fluid in the brain provides a highly regulated environment for central nervous system neurons The brain is physically and metabolically fragile Cerebrospinal Fluid CSF fills the ventricles and subarachnoid space The brain floats in CSF, which acts as a shock absorber The choroid plexuses secrete CSF into the ventricles, and the arachnoid granulations absorb it The epithelial cells of the choroid plexus secrete the CSF Brain Extracellular Space Neurons, glia, and capillaries are packed tightly together in the CNS The CSF communicates freely with the BECF, which stabilizes the composition of the neuronal microenvironment The ion fluxes that accompany neural activity cause large changes in extracellular ion concentration The Blood-Brain Barrier The blood-brain barrier prevents some blood constituents from entering the brain extracellular space Continuous tight junctions link brain capillary endothelial cells Uncharged and lipid-soluble molecules more readily pass through the blood-brain barrier Transport by capillary endothelial cells contributes to the blood-brain barrier Glial Cells Glial cells constitute half the volume of the brain and outnumber neurons Astrocytes supply fuel to neurons in the form of lactic acid Astrocytes are predominantly permeable to K+ and also help regulate [K+]o Gap junctions couple astrocytes to one another, allowing diffusion of small solutes Astrocytes synthesize neurotransmitters, take them up from the extracellular space, and have neurotransmitter receptors Astrocytes secrete trophic factors that promote neuronal survival and synaptogenesis Astrocytic endfeet modulate cerebral blood flow Oligodendrocytes and Schwann cells make and sustain myelin Oligodendrocytes are involved in pH regulation and iron metabolism in the brain Microglial cells are the macrophages of the CNS References References Books and Reviews Journal Articles Chapter 12 12 Physiology of Neurons Neurons receive, combine, transform, store, and send information Neural information flows from dendrite to soma to axon to synapse Signal Conduction in Dendrites Dendrites attenuate synaptic potentials Dendritic membranes have voltage-gated ion channels Control of Spiking Patterns in the Soma Neurons can transform a simple input into a variety of output patterns Intrinsic firing patterns are determined by a variety of ion currents with relatively slow kinetics Axonal Conduction Axons are specialized for rapid, reliable, and efficient transmission of electrical signals Action potentials are usually initiated at the initial segment Conduction velocity of a myelinated axon increases linearly with diameter Demye