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A Study Of The Mechanism Of Ion Channel Voltage Sensing In The Shaker Potassium Channel
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Book Synopsis A Study of the Mechanism of Ion-channel Voltage Sensing in the Shaker Potassium Channel by : Oliver Samuel Baker
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:
Book Synopsis Mechanisms of ion channels voltage-dependency by : Gildas Loussouarn
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.
Book Synopsis Textbook of Ion Channels Volume I by : Jie Zheng
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.
Book Synopsis Understanding the Gating Mechanisms of Voltage-dependent Sodium and Potassium Channels by : Kevin M. Oelstrom
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.
Book Synopsis Biological Membrane Ion Channels by : Shin-Ho Chung
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.
Book Synopsis Ion Channels and Disease by : Frances M. Ashcroft
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
Book Synopsis Molecular Mechanisms of Voltage-Gating in Ion Channels by : Gildas Loussouarn
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:
Book Synopsis Conformational Changes during Potassium-Channel Gating by : Jakob Renhorn
Download or read book Conformational Changes during Potassium-Channel Gating written by Jakob Renhorn and published by Linköping University Electronic Press. This book was released on 2018-04-09 with total page 71 pages. Available in PDF, EPUB and Kindle. Book excerpt: Voltage-gated ion channels have a paramount importance in many physiological processes such as cell-to-cell communication, action potential-propagation, and cell motility. Voltage-gated ion channels are characterized by their ability to sense membrane voltage and to greatly change channel activity in response to small changes in the voltage. The ability to sense voltage resides in the four voltage-sensor domains (VSDs) surrounding the central ion-conducting pore. Membrane depolarization causes the inside of the membrane to become positively charged, electrostatically repelling the positively charged fourth transmembrane segment (S4), or voltage sensor, in the VSD, causing the voltage sensor to move outwards. This motion provides necessary energy to open the pore and allow ion conductivity. Prolonged channel activation leads to alterations in the selectivity filter which cease ion conductivity, in a process called slow inactivation. In this thesis, we investigated the movement of S4 during activation of the channel. We also studied the communication between the four subunits during activation as well as the communication between the pore domain and VSD during slow inactivation. We have shown that voltage sensors move approximately 12 Å outwards during activation. The positively charged amino acid residues in S4 create temporary salt bridges with negative counter-charges in the other segments of the VSD as it moves through a membrane. We have also shown that the movement of one of the four voltage sensors can affect the movement of the neighboring voltage sensors. When at least one voltage sensor has moved to an up-position, it stabilizes other voltage sensors in the up-position, increasing the energy required for the voltage sensor to return to the down position. We have also shown reciprocal communication between the pore domain and the VSDs. Alterations in the VSD or the interface between the pore and the VSD cause changes in the rate of slow inactivation. Likewise, modifications in the pore domain cause changes to the voltage-sensor movement. This indicates communication between the pore and the VSD during slow inactivation. The information from our work could be used to find new approaches when designing channel-modifying drugs for the treatment of diseases caused by increased neuronal excitability, such as chronic pain and epilepsy.
Book Synopsis Textbook of Ion Channels Volume II by : Jie Zheng
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.
Book Synopsis Luminescence Resonance Energy Transfer Studies of the Shaker Potassium Voltage-Gated Ion Channel by :
Download or read book Luminescence Resonance Energy Transfer Studies of the Shaker Potassium Voltage-Gated Ion Channel written by and published by . This book was released on 2005 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Development of Small Molecule Ligands for Voltage-gated Potassium Channels and Functional Characterization of Voltage-gated Phosphatases by : Sarah C. Bell
Download or read book Development of Small Molecule Ligands for Voltage-gated Potassium Channels and Functional Characterization of Voltage-gated Phosphatases written by Sarah C. Bell and published by . This book was released on 2010 with total page 384 pages. Available in PDF, EPUB and Kindle. Book excerpt: Membrane proteins respond to both chemical and electrical stimuli. This work explores the molecular mechanisms by which membrane voltage controls voltage-gated proteins and describes the development of tools to modulate voltage-gated protein function. Voltage-gated potassium (Kv) channels are tetrameric transmembrane proteins that translate changes in the membrane electric field into the controlled permeation of potassium across the plasma membrane. Kv channels mediate the initiation and regulation of action potentials, muscle contraction, hormone secretion, and information processing, rendering them important drug targets. We employed organic synthesis, molecular dynamics and electrophysiology techniques to demonstrate that calix[4]arenes with free phenolic OH groups at the lower rim and positively-charged groups at the upper rim constitute a versatile class of reversible ligands for homotetrameric Kv1.x channels. Synthesis of a panel of calix[4]arenes with variable upper and lower rim substituents enabled the systematic development of Kv1.x channel-compatible ligands. We used molecular modeling to predict calix[4]arene binding to the pore domain, and through electrophysiology experiments, we demonstrated that the calix[4]arene ligands function as reversible blockers of Kv1.x channels. We probed the mechanism of calix[4]arene-channel interactions using voltage clamp fluorometry and found these ligands modify the voltage-dependent motions of the Shaker Kv channel in addition to inhibiting ion current. These calix[4]arene ligands provide a new set of tools to control cell excitability by specifically targeting Kv channels. Until recently, ion channels were the only proteins known to sense changes in membrane potential. This changed with the discovery of Ciona intestinalis voltage-sensor containing phosphatase (Ci-VSP) which has a voltage sensing domain like voltage-gated ion channels and a cytosolic phosphatase domain resembling the phosphoinositide phosphatase PTEN. Ci-VSP is the first member of the voltage dependent family of proteins that is not an ion channel. Instead, Ci-VSP takes an electrical signal in the form of membrane voltage and converts it to a chemical signal through its phosphatase activity. To study the mechanism of voltage-sensing in Ci-VSP, we combined electrophysiology and fluorescence methods in living cells to determine the oligomerization state of Ci-VSP and monitor the functional transitions that result in Ci-VSP mediated changes in phosphoinositide pools. We find that Ci-VSP is a functional monomer which undergoes complex voltage-dependent conformational changes to control a cytosolic phosphoinositide phosphatase domain. As Ci-VSP catalyzes several reactions, we also developed fluorescent-based methods to study Ci-VSP substrate specificity and monitor Ci-VSP-mediated changes in multiple phosphoinositide pools in a single cell. Finally, we find that basic residues in the interdomain linker connecting the voltage sensing domain and phosphatase domains in Ci-VSP are essential for coupling the two domains. Our results indicate that a single voltage sensing domain can function in the membrane on its own and suggests that voltage sensing domains are modular units that can impart voltage sensitivity to a variety of effector domains.
Book Synopsis Ion Channel Pharmacology by : Bernat Soria
Download or read book Ion Channel Pharmacology written by Bernat Soria and published by . This book was released on 1998 with total page 498 pages. Available in PDF, EPUB and Kindle. Book excerpt: The improved understanding of ion channel structure, achieved through the use of molecular biology techniques, has opened the way for the development of new drugs targeted at specific types of ion channels. This book provides a comprehensive, single-volume overview of the effects of different drugs and toxins on ionic channels. The first part of the book deals with the development of ion channels, while subsequent chapters detail the electrophysiological properties and pharmacology of eight different types of ion channels, including intracellular, cyclic nucleotide-gated, and receptor operated channels. Drug effects in various cell types, along with the potential use of channels in therapeutics, are discussed for each channel type. Comprehensive and up-to-date, Ion Channel Pharmacology is an essential reference for every investigator in this fast-growing area of research.
Book Synopsis Studies of the Structure and Gating Mechanism of the KAT1 Voltage-gated Potassium Channel by : Helen C. Lai
Download or read book Studies of the Structure and Gating Mechanism of the KAT1 Voltage-gated Potassium Channel written by Helen C. Lai and published by . This book was released on 2005 with total page 522 pages. Available in PDF, EPUB and Kindle. Book excerpt: KAT1 has the ability to rescue growth of a K+ transporter-deficient yeast strain allowing for rapid screening of thousands of mutant KAT1 channels. Using this assay, we designed a conditional lethal/suppressor screen that could identify interactions between transmembrane segments. This screen identified two highly specific interactions between S4 and S5 of the pore region, indicating close apposition of these regions in the hyperpolarized state of KAT1.
Book Synopsis Pharmacology of Potassium Channels by : Nikita Gamper
Download or read book Pharmacology of Potassium Channels written by Nikita Gamper and published by Springer Nature. This book was released on 2021-09-27 with total page 546 pages. Available in PDF, EPUB and Kindle. Book excerpt: The aim of the present book is to comprehensively review current advances in understanding of genetics, structural biology, pharmacology of potassium channels and their roles in disease as well as to identify current gaps in knowledge. The ultimate goal is to provide a scientific foundation for better understanding of modulatory mechanisms and pharmacology of potassium channels and to use this understanding to drive future drug discovery. This book will be a must-have for academic and industrial scientists interested in physiology, pharmacology, pathology and structure-functional relationships of ion channels. The book will also be helpful for lecturers and students in the college and university classrooms, as well as for anyone interested in the state-of-the art in modern cell biology, physiology and pharmacology.
Book Synopsis Textbook of Ion Channels by : Jie Zheng
Download or read book Textbook of Ion Channels written by Jie Zheng and published by CRC Press. This book was released on 2023-07-06 with total page 1067 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. 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.
Book Synopsis Textbook of Ion Channels Volume III by : Jie Zheng
Download or read book Textbook of Ion Channels Volume III written by Jie Zheng and published by CRC Press. This book was released on 2023-06-28 with total page 246 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 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.
Book Synopsis Molecular Mechanisms of Resin Acids and Their Derivatives on the Opening of a Potassium Channel by : Nina Ottosson
Download or read book Molecular Mechanisms of Resin Acids and Their Derivatives on the Opening of a Potassium Channel written by Nina Ottosson and published by Linköping University Electronic Press. This book was released on 2017-04-20 with total page 66 pages. Available in PDF, EPUB and Kindle. Book excerpt: Voltage-gated ion channels play fundamental roles in excitable cells, such as neurons, where they enable electric signaling. Normally, this signaling is well controlled, but brain damage, alterations in the ionic composition of the extracellular solution, or dysfunctional ion channels can increase the electrical excitability thereby causing epilepsy. Voltage-gated ion channels are obvious targets for antiepileptic drugs, and, as a rule of thumb, excitability is dampened either by closing voltagegated sodium channels (Nav channels) or by opening voltage-gated potassium channels (Kv channels). For example, several classical antiepileptic drugs block the ion-conducting pore of Nav channels. Despite the large number of existing antiepileptic drugs, one third of the patients with epilepsy suffer from intractable or pharmacoresistant seizures. Our research group has earlier described how different polyunsaturated fatty acids (PUFAs) open a Kv channel by binding close to the voltage sensor and, from this position, electrostatically facilitate the movement of the voltage-sensor, thereby opening the channel. However, PUFAs affect a wide range of ion channels, making it difficult to use them as pharmaceutical drugs; it would be desirable to find smallmolecule compounds with an electrostatic, PUFA-like mechanism of action. The aim of the research leading to this thesis was to find, characterize, and refine drug candidates capable of electrostatically opening a Kv channel. The majority of the experiments were performed on the cloned Shaker Kv channel, expressed in oocytes from the frog Xenopus laevis, and the channel activity was explored with the two-electrode voltage-clamp technique. By systematically mutating the extracellular end of the channel’s voltage sensor, we constructed a highly PUFAsensitive channel, called the 3R channel. Such a channel is a useful tool in the search for electrostatic Kv-channel openers. We found that resin acids, naturally occurring in tree resins, act as electrostatic Shaker Kv channel openers. To explore the structure-activity relationship in detail, we synthesized 120 derivatives, whereof several were potent Shaker Kv channel openers. We mapped a common resin acidbinding site to a pocket formed by the voltage sensor, the channel’s third transmembrane segment, and the lipid membrane, a principally new binding site for small-molecule compounds. Further experiments showed that there are specific interactions between the compounds and the channel, suggesting promises for further drug development. Several of the most potent Shaker Kv channel openers also dampened the excitability in dorsal-root-ganglion neurons from mice, elucidating the pharmacological potency of these compounds. In conclusion, we have found that resin-acid derivatives are robust Kv-channel openers and potential drug candidates against diseases caused by hyperexcitability, such as epilepsy.
