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Author: Gildas Loussouarn
Publisher: Frontiers E-books
ISBN: 288919115X
Category :
Languages : en
Pages : 211
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Book Description
Voltage-gated ion channels are transmembrane proteins in which at least one gate is controlled by the transmembrane potential. They are frequently very selectively permeable to sodium (Nav channels), potassium (Kv channels) or calcium (Cav channels) ions. Depending on the channels, opening of the activation gate is triggered by membrane depolarization (Kv, Nav and Cav channels) or hyperpolarization (HCN channels for instance). In addition, in many voltage-gated channels, a so-called inactivation gate is also present. Compared to the activation gate, the latter is oppositely coupled to the potential: In Kv, Nav and Cav channels, upon membrane depolarization, the inactivation gate closes whereas the activation gate opens. Depending on the cell types in which they are expressed and their physiological role, various voltage-dependent channels can be characterized by their conductance, ion selectivity, pharmacology and voltage-sensitivity. These properties are mainly dictated by the amino-acids sequence and structure of the pore forming subunit(s), presence of accessory subunit(s), membrane composition, intra- and extracellular ions concentration. Noteworthy, despite a profound variety of these ion channels characteristics, it seems that most of them obey to the same global, four-fold structure now obtained by several X-ray crystallography experiments. Given the wealth of electrophysiological, biochemical, optical, and structural data regarding ion channels voltage-dependency, we decided to put together in this e-book, up to date reviews describing the molecular details of these complex voltage-gated channels.
Author: Gildas Loussouarn
Publisher: Frontiers E-books
ISBN: 288919115X
Category :
Languages : en
Pages : 211
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Book Description
Voltage-gated ion channels are transmembrane proteins in which at least one gate is controlled by the transmembrane potential. They are frequently very selectively permeable to sodium (Nav channels), potassium (Kv channels) or calcium (Cav channels) ions. Depending on the channels, opening of the activation gate is triggered by membrane depolarization (Kv, Nav and Cav channels) or hyperpolarization (HCN channels for instance). In addition, in many voltage-gated channels, a so-called inactivation gate is also present. Compared to the activation gate, the latter is oppositely coupled to the potential: In Kv, Nav and Cav channels, upon membrane depolarization, the inactivation gate closes whereas the activation gate opens. Depending on the cell types in which they are expressed and their physiological role, various voltage-dependent channels can be characterized by their conductance, ion selectivity, pharmacology and voltage-sensitivity. These properties are mainly dictated by the amino-acids sequence and structure of the pore forming subunit(s), presence of accessory subunit(s), membrane composition, intra- and extracellular ions concentration. Noteworthy, despite a profound variety of these ion channels characteristics, it seems that most of them obey to the same global, four-fold structure now obtained by several X-ray crystallography experiments. Given the wealth of electrophysiological, biochemical, optical, and structural data regarding ion channels voltage-dependency, we decided to put together in this e-book, up to date reviews describing the molecular details of these complex voltage-gated channels.
Author: Jie Zheng
Publisher: CRC Press
ISBN: 1000857751
Category : Medical
Languages : en
Pages : 331
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Book Description
The Textbook of Ion Channels is a set of three volumes providing a wide-ranging reference source on ion channels for students, instructors and researchers. Ion channels are membrane proteins that control the electrical properties of neurons and cardiac cells; mediate the detection and response to sensory stimuli like light, sound, odor, and taste; and regulate the response to physical stimuli like temperature and pressure. In non-excitable tissues, ion channels are instrumental for the regulation of basic salt balance that is critical for homeostasis. Ion channels are located at the surface membrane of cells, giving them the unique ability to communicate with the environment, as well as the membrane of intracellular organelles, allowing them to regulate internal homeostasis. Ion channels are fundamentally important for human health and diseases, and are important targets for pharmaceuticals in mental illness, heart disease, anesthesia, pain and other clinical applications. The modern methods used in their study are powerful and diverse, ranging from single ion-channel measurement techniques to models of ion channel diseases in animals, and human clinical trials for ion channel drugs. Volume I, Part 1 covers fundamental topics such as the basic principles of ion permeation and selectivity, voltage-dependent, ligand-dependent, and mechano-dependent ion channel activation mechanisms, the mechanisms for ion channel desensitization and inactivation, and basic ion channel pharmacology and inhibition. Volume I, Part 2 offers a practical guide of cardinal methods for researching ion channels, including heterologous expression and voltage-clamp and patch-clamp electrophysiology; isolation of native currents using patch clamping; modeling ion channel gating, structures, and its dynamics; crystallography and cryo-electron microscopy; fluorescence and paramagnetic resonance spectroscopy methods; and genetics approaches in model organisms. All three volumes give the reader an introduction to fundamental concepts needed to understand the mechanism of ion channels; a guide to the technical aspects of ion channel research; a modern guide to the properties of major ion channel families; and includes coverage of key examples of regulatory, physiological and disease roles for ion channels.
Author: Gildas Loussouarn
Publisher: Frontiers Media SA
ISBN: 2889715884
Category : Science
Languages : en
Pages : 163
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Book Description
Author:
Publisher:
ISBN: 9780815332183
Category : Cells
Languages : en
Pages : 0
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Book Description
Author: Juliusz Ashot Kozak
Publisher: CRC Press
ISBN: 149875273X
Category : Science
Languages : en
Pages : 343
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Book Description
Calcium Entry Channels in Non-Excitable Cells focuses on methods of investigating the structure and function of non-voltage gated calcium channels. Each chapter presents important discoveries in calcium entry pathways, specifically dealing with the molecular identification of store-operated calcium channels which were reviewed by earlier volumes in the Methods in Signal Transduction series. Crystallographic and pharmacological approaches to the study of calcium channels of epithelial cells are also discussed. Calcium ion is a messenger in most cell types. Whereas voltage gated calcium channels have been studied extensively, the non-voltage gated calcium entry channel genes have only been identified relatively recently. The book will fill this important niche.
Author: Valentin K. Gribkoff
Publisher: John Wiley & Sons
ISBN: 0470429895
Category : Science
Languages : en
Pages : 505
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Book Description
This book discusses voltage-gated ion channels and their importance in drug discovery and development. The book includes reviews of the channel genome, the physiological bases of targeting ion channels in disease, the unique technologies developed for ion channel drug discovery, and the increasingly important role of ion channel screening in cardiac risk assessment. It provides an important reference for research scientists and drug discovery companies.
Author: Kevin M. Oelstrom
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Complex multicellular organisms need a communication network that links distant parts of the organism and allows information to be rapidly transmitted between these regions. This task is accomplished by electrochemical signaling through excitable cells and is regulated by ion channels that allow selective passage of different charged species through their transmembrane pores depending on numerous conditions. A specific kind of ion channel, a voltage-gated ion channel, allows sodium, calcium or potassium to move across either side of the membrane when a change in the membrane potential directly influences the channel and ultimately opens its pore gate. This thesis focuses on two aspects of this process; the location and composition of the gate in a voltage-dependent sodium channel and the mechanism by which a change in voltage can be sensed by a channel and then have this information transmitted through the protein to the gate, prompting it to open. By substituting individual cysteine residues into the lower S6 helices of domains I-IV of a voltage-gated sodium channel and measuring their state-dependent accessibility to a membrane-impermeant thiol-modifying reagent, it was demonstrated that the gate in this channel type is located near the cytoplasmic end of the pore and is minimally composed of four bulky hydrophobic amino acids. After measuring gating currents for numerous single and double alanine mutant pairs and using this information to calculate the change in free energy of activation for each mutant, multiple interaction networks were identified in different regions of the Shaker potassium channel that are involved in the process of transmitting the energy associated with voltage-sensing to the channel gate. Results will be discussed within the context of relevant structural information.
Author: Peter C. Ruben
Publisher: Springer Science & Business Media
ISBN: 3642415881
Category : Medical
Languages : en
Pages : 328
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Book Description
A number of techniques to study ion channels have been developed since the electrical basis of excitability was first discovered. Ion channel biophysicists have at their disposal a rich and ever-growing array of instruments and reagents to explore the biophysical and structural basis of sodium channel behavior. Armed with these tools, researchers have made increasingly dramatic discoveries about sodium channels, culminating most recently in crystal structures of voltage-gated sodium channels from bacteria. These structures, along with those from other channels, give unprecedented insight into the structural basis of sodium channel function. This volume of the Handbook of Experimental Pharmacology will explore sodium channels from the perspectives of their biophysical behavior, their structure, the drugs and toxins with which they are known to interact, acquired and inherited diseases that affect sodium channels and the techniques with which their biophysical and structural properties are studied.
Author: Frances M. Ashcroft
Publisher: Academic Press
ISBN: 0080535216
Category : Science
Languages : en
Pages : 505
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Book Description
Ion channels are membrane proteins that act as gated pathways for the movement of ions across cell membranes. They play essential roles in the physiology of all cells. In recent years, an ever-increasing number of human and animal diseases have been found to result from defects in ion channel function. Most of these diseases arise from mutations in the genes encoding ion channel proteins, and they are now referred to as the channelopathies. Ion Channels and Disease provides an informative and up-to-date account of our present understanding of ion channels and the molecular basis of ion channel diseases. It includes a basic introduction to the relevant aspects of molecular biology and biophysics and a brief description of the principal methods used to study channelopathies. For each channel, the relationship between its molecular structure and its functional properties is discussed and ways in which genetic mutations produce the disease phenotype are considered. This book is intended for research workers and clinicians, as well as graduates and advanced undergraduates. The text is clear and lively and assumes little knowledge, yet it takes the reader to frontiers of what is currently known about this most exciting and medically important area of physiology. - Introduces the relevant aspects of molecular biology and biophysics - Describes the principal methods used to study channelopathies - Considers single classes of ion channels with summaries of the physiological role, subunit composition, molecular structure and chromosomal location, plus the relationship between channel structure and function - Looks at those diseases associated with defective channel structures and regulation, including mutations affecting channel function and to what extent this change in channel function can account for the clinical phenotype
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Voltage-gated ion channels (VGICs) constitute an evolutionary diverse family of integral membrane proteins that transport ions across the hydrophobic membrane bilayers, when triggered by changes in membrane potential. This thesis examines the manifestations of the fundamental laws of thermodynamics on this family of proteins to understand how they operate at the molecular level. In the first few Chapters of this thesis, I describe an analytical approach to extract the energetics of voltage-dependent activation of ion channels and use it to determine the interaction energies between residues in the exemplar Shaker KV channel. The approach involves extracting a special parameter, the median voltage of activation (VM) from experimentally measured gating-charge displacement vs voltage (QV) curves. Next, I use this approach to determine the interaction energies between residues comprising an intersubunit gating nexus, which is likely to be crucial for the relay of structural and energetic information, from the voltage-sensors to the pore. Additionally, I describe how these thermodynamic principles can be extended to deconstruct the allosteric linkage pathways between voltage and ligand dependent activation pathways of polymodal allosteric channels. In the final chapter of this thesis, I study the mechanism by which temperature modulates voltage-dependent gating of ion channels. Gating of some members of the VGIC superfamily is exquisitely sensitive to changes in temperature, however we lack an understanding of the molecular mechanisms underlying temperature sensation and modulation of voltage-dependent channel function. I use a heuristic approach to systematically engineer mutations into the relatively temperature insensitive Shaker KV channel to design a temperature modulated voltage-dependent channel. From the characterization of the relative open probability vs voltage curves of over fifty mutants of the channel at two different temperatures, I propose that thermal sensitivity is mediated by state dependent changes in the solvation status of critical residues, which governs CP of channel gating. I also demonstrate that voltage-sensing charges play a crucial although indirect role in governing the effect of temperature on channel gating. These principles could be very useful to deconstruct the temperature sensing mechanisms of natively thermosensitive channels, such as the thermoTRPs and other structurally unrelated channels, such as Anoctamins.
