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 137 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 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 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 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 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 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 Voltage gated Sodium Channels Structure Function and Channelopathies written by Mohamed Chahine and published by Springer. This book was released on 2018-06-04 with total page 448 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a timely state-of-the-art overview of voltage-gated sodium channels, their structure-function, their pharmacology and related diseases. Among the topics discussed are the structural basis of Na+ channel function, methodological advances in the study of Na+ channels, their pathophysiology and drugs and toxins interactions with these channels and their associated channelopathies.
Download or read book Handbook of Ion Channels written by Jie Zheng and published by CRC Press. This book was released on 2015-02-25 with total page 682 pages. Available in PDF, EPUB and Kindle. Book excerpt: The New Benchmark for Understanding the Latest Developments of Ion ChannelsIon channels control the electrical properties of neurons and cardiac cells, mediate the detection and response to sensory stimuli, and regulate the response to physical stimuli. They can often interact with the cellular environment due to their location at the surface of ce
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 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 Neuronal Dynamics written by Wulfram Gerstner and published by Cambridge University Press. This book was released on 2014-07-24 with total page 591 pages. Available in PDF, EPUB and Kindle. Book excerpt: This solid introduction uses the principles of physics and the tools of mathematics to approach fundamental questions of neuroscience.
Download or read book Broadband Tuning the Voltage Dependence of a Sodium Channel written by Eedann McCord and published by . This book was released on 2019 with total page 101 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mammalian voltage-gated sodium channels are comprised of four homologous domains, each containing a functionally distinct voltage-sensing domain (VSD). In contrast, the bacterial sodium channel NaVAb is a homotetramer, which enables investigation into the voltage-dependent gating mechanism without needing to account for heterogenic VSD contributions to the total signal. We endeavored to alter the properties of the VSD such that it moves in response to voltage changes over a wide range of voltages. By shifting the voltage dependence of activation in this manner, the channels can be used a means to better understand the structural features that control voltage sensing. We hypothesized that a VSD that activates only at voltages above 0 mV could be used as a tool to study the resting state with structural biology and further our understanding of the structural basis of voltage sensation. Human NaV1.7 has been identified as a drug target for the treatment of a multitude of pain disorders, thus we created several chimeric channels with human NaV1.7 DII residues comprising the extracellular portion of the VSD and NaVAb residues in the S0, S4-S5 linker, and pore domain. Channels with entirely human VSDs and ones wherein the human residues extended to the level of the intracellular negative cluster did not show measurable sodium current when transiently transfected into Sf9 cells with a GFP-P2A stoichiometric fluorescent indicator. Less humanized VSDs were functional and displayed a range of voltage-dependencies of activation V1/2 values and opening rates. Several single amino-acid substitutions whose effects were studied in other sodium and potassium channels further modified the voltage-dependence of gating in these chimeras. The combinatorial effect of these substitutions on activation was examined, and it was found that by combining mutations that produce strong effects on their own, drastic shifts in the voltage dependence of channel opening could be seen. In several cases, this did not translate to a substantial change in the voltage dependence of the gating charge movement itself, but it is possible that intermediate states were stabilized and impeded the fast movement of the voltage sensor. One combination of triple mutations, however, shifted channel opening and charge movement to more positive potentials, and this was used in combination with intersubunit disulfide crosslinking to stabilize a resting state of the voltage sensor in a cryo-EM structure at a resolution of 3.9 [Angstroms] . This structure showed an 11 [Angstroms] downward movement of the of the gating charges which is consistent with the sliding helix model of voltage sensor activation. The S4-S5 linker moves 9.6 [Angstroms] in the gating process as it constricts around the base of the pore and sterically prevents its opening. These findings enhance our understanding of the voltage sensation process and its translation to the opening of the pore of sodium channels.
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.
Download or read book Ion Channels in Health and Sickness written by Fatima Shad Kaneez and published by BoD – Books on Demand. This book was released on 2018-10-10 with total page 204 pages. Available in PDF, EPUB and Kindle. Book excerpt: Ion channels are proteins that make pores in the membranes of excitable cells present both in the brain and the body. These cells are not only responsible for converting chemical and mechanical stimuli into the electrical signals but are also liable for monitoring vital functions. All our activities, from the blinking of our eyes to the beating of our heart and all our senses from smell to sight, touch, taste and hearing are regulated by the ion channels. This book will take us on an expedition describing the role of ion channels in congenital and acquired diseases and the challenges and limitations scientist are facing in the development of drugs targeting these membrane proteins.
Download or read book Computing Characterizations of Drugs for Ion Channels and Receptors Using Markov Models written by Aslak Tveito and published by Springer. This book was released on 2016-04-19 with total page 279 pages. Available in PDF, EPUB and Kindle. Book excerpt: Flow of ions through voltage gated channels can be represented theoretically using stochastic differential equations where the gating mechanism is represented by a Markov model. The flow through a channel can be manipulated using various drugs, and the effect of a given drug can be reflected by changing the Markov model. These lecture notes provide an accessible introduction to the mathematical methods needed to deal with these models. They emphasize the use of numerical methods and provide sufficient details for the reader to implement the models and thereby study the effect of various drugs. Examples in the text include stochastic calcium release from internal storage systems in cells, as well as stochastic models of the transmembrane potential. Well known Markov models are studied and a systematic approach to including the effect of mutations is presented. Lastly, the book shows how to derive the optimal properties of a theoretical model of a drug for a given mutation defined in terms of a Markov model.
Download or read book Structures and Mechanisms of Gating in Shaker Voltage dependent Potassium Channels written by Sarah MacKenzie Webster and published by . This book was released on 2003 with total page 202 pages. Available in PDF, EPUB and Kindle. Book excerpt:
