Molecular and Cellular Physiology of Neurons, Second Edition

Molecular and Cellular Physiology of Neurons, Second Edition

GORDON L. FAIN
with THOMAS J. O’DELL
Illustrations by Margery J. Fain
Copyright Date: 2014
Published by: Harvard University Press
Pages: 740
https://www.jstor.org/stable/j.ctt1287gn2
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  • Book Info
    Molecular and Cellular Physiology of Neurons, Second Edition
    Book Description:

    Gordon Fain'sMolecular and Cellular Physiology of Neurons, Second Editionis intended for anyone who seeks to understand nerve cell function: undergraduate and graduate students in neuroscience, students of bioengineering and cognitive science, and practicing neuroscientists who want to deepen their knowledge of recent discoveries.

    eISBN: 978-0-674-73564-4
    Subjects: Biological Sciences

Table of Contents

  1. Front Matter
    (pp. i-vi)
  2. Table of Contents
    (pp. vii-viii)
  3. Preface
    (pp. ix-xiv)
  4. 1 Introduction
    (pp. 1-28)

    The basic premise of this book is that we need to know how individual molecules and cells produce neural activity in order to understand the brain. It may not be obvious why this should be so. After all, it is not particularly important for us to understand the detailed functioning of diodes or transistors to comprehend how a computer is programmed. Why do we need to know about the molecules and cells of the nervous system?

    For those of us who have spent our scientific careers studying sensory receptors and neural integration in the central nervous system (CNS), the importance...

  5. PART ONE Electrical Properties of Cells and Homeostasis
    • 2 Electrical Properties of Neurons
      (pp. 31-69)

      A nerve cell integrates incoming signals by performing simple calculations. It adds and subtracts inputs from excitatory and inhibitory synapses, and the results of these calculations are reflected in the output that the cell transmits to other cells. For the pyramidal cell in Fig. 1.1, there are many excitatory synapses onto spines (Fig. 1.1C), and the changes in membrane potential at these synapses are summed and communicated to other parts of the dendritic tree and to the cell body and axon. If the changes in potential are large enough and of the right polarity, the axon produces action potentials, which...

    • 3 Ion Permeability and Membrane Potentials
      (pp. 70-106)

      Sensory detection, higher mental function and consciousness all have their basis in electrical signals produced by changes in voltage across the plasma membrane of nerve cells. These changes in voltage are produced when the resting membrane potential, which is typically of the order of −60 mV to −70 mV, is altered by the opening or closing of ion channels. Channels act as gates, which can be opened by voltage or the binding of transmitters and which allow entry only to certain ions such as Na+or Cl.

      For neurons and other cells in the body, all of the ions of...

    • 4 Ion Pumps and Homeostasis
      (pp. 107-142)

      The asymmetric ion concentrations that generate the driving forces for ion movement are produced by pumps and transporters, which move ions into or out of the cell. Membrane proteins such as the Na+/K+ATPase use the high-energy bond of the terminal phosphate of ATP to move Na+and K+across the plasma membrane, creating the unequal distributions of these ions that drive Na+and K+currents during action potentials and excitatory synaptic stimulation. Other transporters establish gradients for Ca2+, Cl, and H+(that is, for pH). In this chapter, we review the structure and function of these proteins and the...

  6. PART TWO Active Propagation of Neural Signals
    • 5 Action Potentials: The Hodgkin-Huxley Experiments
      (pp. 145-191)

      The passive spread or decremental conduction of electrical signals down the axons and dendrites of nerve cells described in Chapter 2 is one way messages can be communicated from one part of the nervous system to another. Passive spread is essential for the conveyance of synaptic potentials within the dendritic tree, and some neurons (like the starburst amacrine cell of Plate Fig. 2.2) appear to use only decremental conduction to transmit electrical signals. These cells are probably exceptions. Many neurons in the CNS are too large to be able to rely only on passive spread. Pyramidal cells can have long...

    • 6 The Structure and Function of Voltage-Gated Na+ and K+ Channels
      (pp. 192-230)

      The hodgkin-huxley model was intended to be a quantitative description of the voltage and time dependence of the Na+and K+conductances. Although Hodgkin and Huxley were doubtful that their calculations would provide any insight into the molecular details of gating, subsequent research has shown that many of their assumptions and conclusions are substantially correct. There is overwhelming evidence that Na+and K+pass through separate channels with different ion selectivity, pharmacology, and structure. Na+and K+channel genes have been isolated, cloned, and sequenced; they are clearly members of different families coding for distinct, although related, proteins.

      Hodgkin and...

    • 7 The Diversity of Ion Channels
      (pp. 231-278)

      The mammalian genome has genes for at least nine different Na+channels and perhaps as many as seventy different kinds of K+channels. In addition, neurons contain a wide variety of voltage-gated Ca2+channels, nonselective cationic channels, and channels permeable to Cl. Why are there so many different kinds? In part this is because different channel types have different physiological properties, which are likely to have important effects on action potential threshold, firing rates, and the voltage and time dependence of synaptic transmitter release. In this chapter we describe some of the major channel types, emphasizing those we believe to...

  7. PART THREE Synaptic Transmission and Ligand-Gated Channels
    • 8 Presynaptic Mechanisms of Synaptic Transmission
      (pp. 281-327)
      Thomas J. O’Dell

      Part 3 of this book describes the fundamental basis of nerve cell communication: the physiology of synaptic transmission. Synapses are the specialized contacts between neurons and target cells where information is transmitted from one cell to the next. Understanding how they work is absolutely essential for understanding how signals travel from one cell to another and how information is processed within the CNS. Synapses are also the sites where neuromodulatory mechanisms act to store information during learning and memory formation. Finally, the proteins responsible for synaptic transmission are targets of many psychoactive drugs.

      Although several different kinds of cellular communication...

    • 9 Excitatory Transmission
      (pp. 328-384)

      Chemical communication in the nervous system can occur in two ways. Small molecular-weight neurotransmitters (Fig. 9.1) released by a presynaptic cell can bind to receptors that are themselves ion channels (calledligand-gated receptorsorionotropic receptors). There are several major families of such proteins, including excitatory nicotinic acetylcholine (ACh) and glutamate receptors, which we describe in this chapter; and inhibitory GABAAand glycine receptors, covered in Chapter 10. There are, in addition, 5-HT3ligand-gated receptors for 5-hydroxytryptamine (or serotonin—see Lummis, 2012), as well as P2X receptors for ATP (Browne et al., 2010) and ionotropic receptors for histamine in invertebrates...

    • 10 Inhibitory Transmission
      (pp. 385-414)
      Thomas J. O’Dell

      The output of a neuron is determined not only by excitatory synapses releasing ACh and glutamate but also by a large and physiologically important inhibitory input. The most important sources of inhibition in the CNS are mediated by receptors for the transmitters γ-aminobutyric acid (GABA) and glycine (Fig. 9.1). These two receptor classes comprise all of the inhibitory ligand-gated channels of vertebrates, and together they are responsible for all rapid inhibitory transmission. In addition, activation of a number of different metabotropic receptors can mediate inhibition in the CNS, and some of these receptors and their G-protein-linked pathways are described in...

    • Color illustrations
      (pp. None)
  8. PART FOUR Metabotropic Transmission and Neuromodulation
    • 11 Metabotropic Transmission: Receptors and G Proteins
      (pp. 417-440)

      In addition to the ionotropic receptors we have described in Chapters 9 and 10, neurons can express metabotropic receptors, which are not themselves ion channels. Metabotropic receptors are ubiquitous in the nervous system and have essential roles in nearly every aspect of CNS function. Activation of these receptors can gate ion channels indirectly or regulate the activity of protein kinases and phosphatases, enzymes that phosphorylate or dephosphorylate proteins and alter their properties. The placing or removing of one or more negatively charged phosphate groups onto particular sites in a protein structure can cause a significant change in conformation, as amino...

    • 12 Metabotropic Transmission: Effector Molecules
      (pp. 441-475)

      Activated G protein, either as Gα · GTP or Gβγ, dissociates from receptor and diffuses near to or within the membrane to target proteins calledeffectors. Gα · GTP and Gβγ bind directly to the effectors and regulate their activity, translating G-protein activation into some alteration in the physiology of the cell. Activated G protein can influence more than one effector. Gαican inhibit adenylyl cyclase, and Gαqcan activate PLCβ; but the Gβγ released from Gα · GTP can also stimulate or inhibit adenylyl cyclase and activate PLCβ, as well as gate the opening of K+channels or inhibit...

    • 13 Metabotropic Transmission: Calcium
      (pp. 476-508)

      Cyclic nucleotides and DAG affect nearly every aspect of nerve cell function, but calcium is at least as important a second messenger in the CNS (Berridge, 2009; Grienberger and Konnerth, 2012). It can enter the cytoplasm through voltage-gated calcium channels, transient receptor-potential (TRP) channels, or cyclic-nucleotidegated channels, as well as through glutamate or ACh receptors. It can be released from intracellular stores in endoplasmic reticulum (ER) by metabotropic transmitters and G-protein-coupled receptors. An increase in Ca2+, often in association with the Ca2+-binding protein calmodulin, can alter the activity of many other proteins in nerve cells. These include the important kinase...

    • 14 Long-Term Potentiation
      (pp. 509-542)
      Thomas J. O’Dell

      The strength or efficacy of synaptic transmission at many excitatory synapses in the brain is not fixed but is instead modulated over a time scale of seconds to minutes by neurotransmitters, which act through many of the G-protein-mediated second messenger pathways described in Chapters 11–13. In addition to these relatively short-lived regulatory influences, synaptic transmission at many synapses can also be modified on a much longer time scale, ranging from many hours to several weeks or more. These longer-lasting changes in synaptic strength are induced by certain patterns of synaptic activity and are thought to provide a cellular mechanism...

  9. PART FIVE Sensory Transduction
    • 15 Mechanoreceptors
      (pp. 545-582)

      Sensory receptor cells are specialized for the detection of an external stimulus such as light or sound and are often found in highly developed organs like the eye or ear. Sensory cells contain molecules that convert an external stimulus into an electrical signal by a process calledsensory transduction. The mechanism of transduction in different receptor cells provides a con ve nient means of dividing them into two classes, which we shall callionotropicandmetabotropicby analogy to the mechanisms of signal transduction at the postsynaptic membrane. For some sensory receptors, external stimuli act directly on ion channels to...

    • 16 Photoreceptors and Olfactory Receptor Neurons
      (pp. 583-628)

      For the second class of sensory receptors, a sensory signal stimulates a G protein and initiates a transduction cascade instead of activating a channel directly. The two most thoroughly studied metabotropic sensory receptor cells are vertebrate photoreceptors and vertebrate olfactory receptor neurons, which work in a similar way. For both, the sensory signal (light or odor) is detected by one of a specialized group of G-protein-coupled receptors, similar in design to those described in Chapter 11. The receptor protein then interacts with a G protein, which activates an effector molecule to produce a change in the concentration of a second...

  10. Appendix: Symbols Used
    (pp. 629-632)
  11. References
    (pp. 633-722)
  12. Index
    (pp. 723-735)