Thermodynamics Of Voltage Dependent Gating Of Ion Channels
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Thermodynamics Of Voltage Dependent Gating Of Ion Channels
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Author :
language : en
Publisher:
Release Date : 2015
Thermodynamics Of Voltage Dependent Gating Of Ion Channels written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015 with categories.
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.
Towards A Physical Understanding Of Thermodynamic And Kinetic Properties Of Gating In Voltage Dependent Ion Channels
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Author : Daniel Sigg
language : en
Publisher:
Release Date : 1999
Towards A Physical Understanding Of Thermodynamic And Kinetic Properties Of Gating In Voltage Dependent Ion Channels written by Daniel Sigg and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1999 with categories.
Molecular Mechanisms Of Voltage Gating In Ion Channels
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Author : Gildas Loussouarn
language : en
Publisher: Frontiers Media SA
Release Date : 2021-11-03
Molecular Mechanisms Of Voltage Gating In Ion Channels written by Gildas Loussouarn and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021-11-03 with Science categories.
Mechanisms Of Mode Shift And Gating Polarity In Voltage Dependent Ion Channels
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Author : John Cowgill
language : en
Publisher:
Release Date : 2020
Mechanisms Of Mode Shift And Gating Polarity In Voltage Dependent Ion Channels written by John Cowgill and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020 with categories.
Electrical signaling is one of the most essential processes to the survival of higher organisms. This is mediated by the regulated flow of ions through the cell membrane catalyzed by a diverse set of membrane proteins known as ion channels. An important channel type opens and closes in response to changes in the membrane potential. These voltage-gated ion channels (VGICs) thus regulate the very stimulus which governs their activity, enabling them to generate and regulate electrical excitability in cells. In this thesis, I examine the structural and thermodynamic aspects of voltage-dependent regulation of channel function. In Chapter Three, I used a hierarchical approach based on recently-solved cryoEM structures of two VGICs to examine the role of various structural elements in voltage sensing, opening the pore, and coupling these processes. I localized discrete elements in hyperpolarization-activated cyclic nucleotide-regulated (HCN) channels that are responsible for conferring an inverted gating response in these channels compared to virtually all other VGICs which activate on depolarization. Surprisingly, the HCN voltage sensor can gate the same pore open in both hyperpolarizing and depolarizing directions suggesting that these channels use a unique voltage sensing mechanism. In Chapter Four, long-timescale molecular dynamics simulations from collaborators revealed a new atomic model of voltage sensing in HCN channels that sheds light on the mechanism of inverted gating polarity. We experimentally validated this novel mechanism using cysteine accessibility measurements and utilized our bipolar constructs to demonstrate that this mechanism underlies the inverted gating polarity of HCN channels. Finally, in Chapter Five I examined the origin mode shift in VGIC gating, a widely observed phenomenon whereby longterm changes in membrane potential alter gating properties. By improving the protocols for recording gating currents, I demonstrated that the hysteresis in gating charge-voltage relationship that is commonly attributed to mode shift stems from non-equilibrium measurement conditions. Throughout these works, my findings are discussed in terms of structural, functional, and thermodynamic implications.
Textbook Of Ion Channels Volume I
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Author : Jie Zheng
language : en
Publisher: CRC Press
Release Date : 2023-06-09
Textbook Of Ion Channels Volume I written by Jie Zheng and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2023-06-09 with Medical categories.
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.
Mechanisms Of Ion Channels Voltage Dependency
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Author : Gildas Loussouarn
language : en
Publisher: Frontiers E-books
Release Date :
Mechanisms Of Ion Channels Voltage Dependency written by Gildas Loussouarn and has been published by Frontiers E-books this book supported file pdf, txt, epub, kindle and other format this book has been release on with categories.
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.
Trp Ion Channel Function In Sensory Transduction And Cellular Signaling Cascades
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Author : Wolfgang B. Liedtke, MD, PH.D.
language : en
Publisher: CRC Press
Release Date : 2006-09-29
Trp Ion Channel Function In Sensory Transduction And Cellular Signaling Cascades written by Wolfgang B. Liedtke, MD, PH.D. and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2006-09-29 with Medical categories.
Since the first TRP ion channel was discovered in Drosophila melanogaster in 1989, the progress made in this area of signaling research has yielded findings that offer the potential to dramatically impact human health and wellness. Involved in gateway activity for all five of our senses, TRP channels have been shown to respond to a wide range of st
Thermodynamics Of Membrane Receptors And Channels
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Author : Meyer B. Jackson
language : en
Publisher: CRC Press
Release Date : 1992-11-18
Thermodynamics Of Membrane Receptors And Channels written by Meyer B. Jackson and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 1992-11-18 with Science categories.
Thermodynamics of Membrane Receptors and Channels synthesizes a wealth of new information regarding the biophysics of membrane proteins. New insights provided by molecular genetics, single channel recording, and high resolution structural techniques are discussed from a conceptual perspective. Basic theoretical topics are introduced, developed, and then extensively illustrated with recent results from the literature or data from the authors' own laboratories. Theoretical and experimental information is incorporated into in-depth discussions of ion permeation mechanisms, ion channel and receptor conformational changes, aggregate activity of complexes of lipids and proteins, and how coupling is achieved between different energy modes in the many transduction systems residing in biomembranes. Thermodynamics of Membrane Receptors and Channels will be valuable both as a learning aid and a reference for biophysicists, neuroscientists, cell biologists, physiologists, and other researchers investigating any aspects of biomembranes.
Textbook Of Ion Channels Volume Iii
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Author : Jie Zheng
language : en
Publisher: CRC Press
Release Date : 2023-06-28
Textbook Of Ion Channels Volume Iii written by Jie Zheng and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2023-06-28 with Medical categories.
The Textbook of Ion Channels is a set of three volumes that provides a wide-ranging reference source on ion channels for students, instructors and researchers. Ion channels are mem- brane proteins that control the electrical properties of neurons and cardiac cells; medi- ate 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 appli- cations. 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 III includes coverage of key ion channel regulators and their mechanisms, the role of ion channels working in concert in selected physiological systems, and examples of ion channel mutations and dysfunction in a selection of diseases. Chapters on ion channel regulation include splice variants, calcium–calmodulin regulation, regulation by G pro- teins, and lipids. A selection of ion channels in physiological systems includes ion chan- nels of the heart, ion channels in immune cells and their role in pancreatic beta cells and regulation of insulin secretion, and the role of channels in sperm and eggs. While disease mechanisms are integrated into the chapters of Volume II, Volume III offers special consid- eration of ion channels in epilepsy, cystic fibrosis and pain syndromes. 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, offer a modern guide to the properties of major ion channel families, and includecoverage of key examples of regulatory, physiological, and disease roles for ion channels.
Ion Channel Factsbook
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Author : William J. Brammar
language : en
Publisher: Academic Press
Release Date : 1998-10-16
Ion Channel Factsbook written by William J. Brammar and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 1998-10-16 with Science categories.
The Academic Press FactsBooks series has established itself as the best source of easily-accessible and accurate facts about protein groups. Described as 'a growing series of excellent manuals' by Molecular Medicine Today, and 'essential works of reference' by Trends in Biochemical Sciences, the FactsBooks have become the most popular comprehensive data resources available. As they are meticulously researched and use an easy-to-follow format, the FactsBooks will keep you up-to-date with the latest advances in structure, amino acid sequences, physicochemical properties, and biological activity.In a set of four interrelated volumes, The Ion Channel FactsBook provides a comprehensive framework of facts about channel molecules central to electrical signaling phenomena in living cells. The fourth volume is devoted to Voltage-gated Channel Families, including those molecular complexes activated or modulated by calcium, potassium, and chloride. Nomenclature Expression Sequence Analyses Structure and function Electrophysiology Pharmacology Information retrieval
