Download or read book Mechanisms of ion channels voltage dependency written by Gildas Loussouarn and published by Frontiers E-books. This book was released on with total page 211 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Textbook of Ion Channels Volume I written by Jie Zheng and published by CRC Press. This book was released on 2023-06-09 with total page 331 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Molecular Mechanisms of Voltage Gating in Ion Channels written by Gildas Loussouarn and published by Frontiers Media SA. This book was released on 2021-11-03 with total page 163 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Molecular Biology of The Cell written by Bruce Alberts and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Structure Function and Modulation of Neuronal Voltage Gated Ion Channels written by Valentin K. Gribkoff and published by John Wiley & Sons. This book was released on 2008-12-09 with total page 505 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Understanding the Gating Mechanisms of Voltage dependent Sodium and Potassium Channels written by Kevin M. Oelstrom and published by . This book was released on 2016 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Voltage Gated Sodium Channels written by Peter C. Ruben and published by Springer Science & Business Media. This book was released on 2014-04-15 with total page 328 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Calcium Entry Channels in Non Excitable Cells written by Juliusz Ashot Kozak and published by CRC Press. This book was released on 2017-07-14 with total page 343 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Ion Channels and Disease written by Frances M. Ashcroft and published by Academic Press. This book was released on 1999-10-20 with total page 505 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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

Download or read book Ion Channels and Plant Stress Responses written by Vadim Demidchik and published by Springer Science & Business Media. This book was released on 2010-03-15 with total page 242 pages. Available in PDF, EPUB and Kindle. Book excerpt: Plants live in a constantly changing environment from which they cannot physically escape. Plants therefore need signalling and response mechanisms to adapt to new local conditions. The ef?cacy of such mechanisms underlies the plant performance during stress and therefore also impacts greatly on agricultural productivity. M- ulation of ion channel activity not only provides a means for rapid signal generation 2+ but also allows adjustment of cellular physiology. For example, Ca permeable ion 2+ channels can transduce environmental stimuli into Ca -encoded messages which can modify the gene expression. Furthermore, ion channel activity is essential to control cellular ion homeostasis that impacts on plant responses to drought, salinity, pathogens, nutrient de?ciency, heavy metals, xenobiotics and other stresses. This volume focuses on the crucial roles of different types of ion channel in plant stress responses. Functions of ion channels are discussed in the context of mechanisms to relay external and endogenous signals during stress and as mechanisms to regulate cellular ion homeostasis and enzymatic activities in the context of biotic and abiotic stress. The chapters presented cover cation and anion channels located in various cellular compartments and tissues.

Download or read book TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades written by Wolfgang B. Liedtke, MD, PH.D. and published by CRC Press. This book was released on 2006-09-29 with total page 502 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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

Download or read book Textbook of Ion Channels Volume II written by Jie Zheng and published by CRC Press. This book was released on 2023-06-28 with total page 489 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Textbook of Ion Channels is a set of three volumes that provides a wide-ranging refer- ence 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-excit- able 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 II starts with ion channel taxonomy and features coverage of major ion channel families, and describes the physiological role, structural components, gating mechanisms and biophysics, permeation and selectivity, regulation, pharmacology, and roles in dis- ease mechanisms. Channels in this volume include voltage-activated sodium, calcium and potassium channels, inward-rectifier and two-pore domain potassium channels, calcium- activated potassium channels, cyclic nucleotide-gated channels, pacemaker ion channels, chloride channels, ligand-gated receptors activated by acetylcholine, glutamate, 5-HT3, GABA and glycine, acid-sensing channels, P2X receptors, TRP channels, store-operated channels, pressure-activated piezo channels, ryanodine receptors, and proton channels. 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 include coverage of key examples of regulatory, physiological and disease roles for ion channels.

Download or read book Site and Mechanism of Action of Resin Acids on Voltage Gated Ion Channels written by Malin Silverå Ejneby and published by Linköping University Electronic Press. This book was released on 2018-05-15 with total page 58 pages. Available in PDF, EPUB and Kindle. Book excerpt: Voltage-gated ion channels are pore-forming membrane proteins that open or close their gates when the voltage across the membrane is changed. They underlie the electrical activity that enables the heart to pump blood and the brain to receive and send signals. Changes in expression, distribution, and functional properties of voltage-gated ion channels can lead to diseases, such as epilepsy, cardiac arrhythmia, and pain-related disorders. Drugs that modulate the function of voltage-gated ion channels control these diseases in some patients, but the existing drugs do not adequately help all patients, and some also have severe side effects. Resin acids are common components of pine resins, with a hydrophobic three-ringed motif and a negatively charged carboxyl group. They open big-conductance Ca2+-activated K+ (BK) channels and voltage-gated potassium (KV) channels. We aimed to characterize the binding site and mechanism of action of resin acids on a KV channel and explore the effect of a resin acid by modifying the position and valence of charge of the carboxyl group. We tested the effect on several voltage-gated ion channels, including two KV channels expressed in Xenopus laevis oocytes and several voltage-gated ion channels expressed in cardiomyocytes. For this endeavour different electrophysiological techniques, ion channels, and cell types were used together with chemical synthesis of about 140 resin-acid derivatives, mathematical models, and computer simulations. We found that resin acids bind between the lipid bilayer and the Shaker KV channel, in the cleft between transmembrane segment S3 and S4, on the extracellular side of the voltage-sensor domain. This is a fundamentally new interaction site for small-molecule compounds that otherwise usually bind to ion channels in pockets surrounded by water. We also showed that the resin acids open the Shaker KV channel via an electrostatic mechanism, exerted on the positively charged voltage sensor S4. The effect of a resin acid increased when the negatively charged carboxyl group (the effector) and the hydrophobic three-ringed motif (anchor in lipid bilayer) were separated by three atoms: longer stalks decreased the effect. The length rule, in combination with modifications of the anchor, was used to design new resin-acid derivatives that open the human M-type (Kv7.2/7.3) channel. A naturally occurring resin acid also reduced the excitability of cardiomyocytes by affecting the voltage-dependence of several voltage-gated ion channels. The major finding was that the resin acid inactivated sodium and calcium channels, while it activated KV channels at more negative membrane voltages. Computer simulations confirmed that the combined effect on different ion channels reduced the excitability of a cardiomyocyte. Finally, the resin acid reversed induced arrhythmic firing of the cardiomyocytes. In conclusion, resin acids are potential drug candidates for diseases such as epilepsy and cardiac arrhythmia: knowing the binding site and mechanism of action can help to fine tune the resin acid to increase the effect, as well as the selectivity.

Download or read book Thermodynamics of Voltage dependent Gating of Ion Channels written by and published by . This book was released on 2014 with total page 308 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Biological Membrane Ion Channels written by Shin-Ho Chung and published by Springer Science & Business Media. This book was released on 2007-11-13 with total page 657 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book deals with recent breakthroughs in ion-channel research that have been brought about by the combined effort of experimental biophysicists and computational physicists, who together are beginning to unravel the story of these exquisitely designed biomolecules. With chapters by leading experts, the book is aimed at researchers in nanodevices and biosensors, as well as advanced undergraduate and graduate students in biology and the physical sciences.

Download or read book A Study of the Mechanism of Ion channel Voltage Sensing in the Shaker Potassium Channel written by Oliver Samuel Baker and published by . This book was released on 1997 with total page 310 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Ionic Channels of Excitable Membranes written by Bertil Hille and published by Sinauer Associates, Incorporated. This book was released on 1992 with total page 638 pages. Available in PDF, EPUB and Kindle. Book excerpt: This new, fully revised and expanded edition of Ionic Channels of Excitable Membranes includes new chapters on fast chemical synapses, modulation through G protein coupled receptors and second messenger systems, molecules cloning, site directed mutagenesis, and cell biology. It begins with the classical biophysical work of Hodgkin and Huxley and then weaves a description of the known ionic channels together with their biological functions. The book continues by developing the physical and molecular principles needed for explaining permeation, gating, pharmacological modification, and molecular diversity, and ends with a discussion of channel evolution. Ionic Channels of Excitable Membranes is written to be accessible and interesting to biological and physical scientists of all kinds.