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| Author | : Osei Kwame Asamoah |
| Publisher | : |
| Total Pages | : 350 |
| Release | : 2004 |
| Genre | : |
| ISBN | : |
| Author | : Valentin K. Gribkoff |
| Publisher | : John Wiley & Sons |
| Total Pages | : 505 |
| Release | : 2008-12-09 |
| Genre | : Science |
| ISBN | : 0470429895 |
This book discusses voltage-gated ion channels and their importance in drug discovery and development. The book includes reviews of the channel genome, the physiological bases of targeting ion channels in disease, the unique technologies developed for ion channel drug discovery, and the increasingly important role of ion channel screening in cardiac risk assessment. It provides an important reference for research scientists and drug discovery companies.
| Author | : James N. C. Kew |
| Publisher | : |
| Total Pages | : 586 |
| Release | : 2010 |
| Genre | : Medical |
| ISBN | : 0199296758 |
Ion channels are intimately involved in the everyday physiological functions that enable us to live a full and varied life. When disease strikes, malfunction of ion channels or their dependent is often involved, either as the cause or the effect of the illness. Thus, billions of dollars have been, and still are being, invested in research to understand the physiological and pathophysiological functions of ion channels in an attempt to develop novel therapeutic treatments for a wide range of diseases. This book provides a comprehensive overview of ion channel structure and function. It comprises two major parts. Part one is an introductory overview of the ion channel superfamily and the generic aspects of ion channel function. This part also reviews the methodologies by which ion channel function can be studied from the perspective of performing detailed biophysical characterization through to the deployment of high throughput approaches for identifying novel ion channel ligands. Part two of the book provides an in-depth review of the individual ion channel subfamilies and, as such, is subdivided into four broad sections: Voltage-Gated Ion Channels, Extracellular Ligand-Gated Ion Channels, Intracellular Ligand-Gated Ion Channels, and Polymodal-Gated Ion Channels, with each chapter focused on specific family members. These chapters have been written by world leading experts and provide a detailed overview of the structure, biophysics, localization, pharmacology, physiology, and disease relevance of each particular ion channel subfamily. Reviewing both the basic principles of ion channel function and providing a detailed up-to-date review of the phsyiological and pharmacological aspects of individual ion channel sub-families, this book constitutes both an excellent introduction to the field for non-specialists, as well as a highly valuable reference text for experienced researchers already working in the ion channel area.
| Author | : Gildas Loussouarn |
| Publisher | : Frontiers E-books |
| Total Pages | : 211 |
| Release | : |
| Genre | : |
| ISBN | : 288919115X |
Voltage-gated ion channels are transmembrane proteins in which at least one gate is controlled by the transmembrane potential. They are frequently very selectively permeable to sodium (Nav channels), potassium (Kv channels) or calcium (Cav channels) ions. Depending on the channels, opening of the activation gate is triggered by membrane depolarization (Kv, Nav and Cav channels) or hyperpolarization (HCN channels for instance). In addition, in many voltage-gated channels, a so-called inactivation gate is also present. Compared to the activation gate, the latter is oppositely coupled to the potential: In Kv, Nav and Cav channels, upon membrane depolarization, the inactivation gate closes whereas the activation gate opens. Depending on the cell types in which they are expressed and their physiological role, various voltage-dependent channels can be characterized by their conductance, ion selectivity, pharmacology and voltage-sensitivity. These properties are mainly dictated by the amino-acids sequence and structure of the pore forming subunit(s), presence of accessory subunit(s), membrane composition, intra- and extracellular ions concentration. Noteworthy, despite a profound variety of these ion channels characteristics, it seems that most of them obey to the same global, four-fold structure now obtained by several X-ray crystallography experiments. Given the wealth of electrophysiological, biochemical, optical, and structural data regarding ion channels voltage-dependency, we decided to put together in this e-book, up to date reviews describing the molecular details of these complex voltage-gated channels.
| Author | : Jeffrey J. Clare |
| Publisher | : John Wiley & Sons |
| Total Pages | : 302 |
| Release | : 2006-08-21 |
| Genre | : Science |
| ISBN | : 3527607935 |
Filling the gap created over the past five years, during which many new techniques have entered the market, this book is directed at both the new and the experienced ion channel researcher wishing to learn more about the considerations and methods for studying recombinant ion channels. These latest developments are covered here for the first time, contributed by editors and authors working for major pharmaceutical companies and who routinely apply these techniques in their daily work. The first three chapters cover the use of the Xenopus oocyte expression system for structure-function studies, from basic approaches for manipulating ion channel cDNAs to more specialized but powerful techniques. This is followed by reviews of strategies and methodologies available for expressing channels in mammalian cells and for their analysis by patch-clamp electrophysiology. Chapters 6 to 8 review the latest methodologies for ion channel drug discovery, including high throughput screening using fluorescence and luminescence, as well as automated planar array electrophysiology. The remaining two chapters focus on approaches for determining ion channel crystal structures and on computational approaches to understanding channel mechanisms at atomic resolution. Rather than provide detailed protocols, indicated by references in each chapter, the authors provide a comprehensive and easily accessible overview of the techniques involved, reviewing underlying principles and providing working guidelines as well as an understanding of the key theoretical and practical considerations associated with each topic. In each case, this practical advice is illustrated by real life examples, taken either from the author's own experience or from key examples in the literature, providing valuable practical hints not found elsewhere. The result is a compendium of practical ion channel information that will prove a valuable resource to academic and industrial workers alike.
| Author | : D. Peter Tieleman |
| Publisher | : |
| Total Pages | : 207 |
| Release | : 2001 |
| Genre | : |
| ISBN | : |
| Author | : |
| Publisher | : Academic Press |
| Total Pages | : 422 |
| Release | : 2021-06-05 |
| Genre | : Science |
| ISBN | : 0323853773 |
Ion Channels Part B, Volume 652 in the Methods in Enzymology series, highlights new advances in the field, with this new volume presenting interesting chapters on a variety of topics, including NMDAR, Pannexin, and CALHM, Making NaV1.4 and NaV1.7, TRPVs, Purification native nAChRs, GABAR Radu Aricescu, TRPV5/2, NaV1.5, KATP, TRPA1, TREK-1, SARS-CoV-2 3a ion channel, Ion channel conformational dynamics by encoded unnatural amino acid, Fluorescence lifetime measurement of absolute membrane potential, Fluorescent Toxins as Activity Sensors, FRET Analyses of Ion Channel Protein-Protein Interactions, Control of Ion Channel Gating with Photo-Switchable Tweezers, and Counting Subunits in Kv Channel Complexes. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Methods in Enzymology series
| Author | : David J. Aidley |
| Publisher | : Cambridge University Press |
| Total Pages | : 324 |
| Release | : 1996-08-13 |
| Genre | : Medical |
| ISBN | : 9780521498821 |
Ion channels are crucial components of living cells. Situated in the cell's membranes. they allow particular ions to pass from one side of the membrane to the other. In recent years the patch clamp technique has allowed the activity of individual channels to be measured, and recombinant DNA technology has led to fascinating detail on their structure. Together, these technical advances have produced a great flowering of knowledge and understanding about the subject, itself leading to further breakthroughs in science and medicine. Ion Channels provides an introduction to this scientific endeavour. It emphasises the molecular structure of channels as determined by gene cloning technology. This knowledge illuminates discussions of the permeability and selectivity of channels, their gating and modulation, their responses to drugs and toxins and the human diseases caused when they do not function properly.
| Author | : Guy M. P. Coates |
| Publisher | : |
| Total Pages | : 240 |
| Release | : 2001 |
| Genre | : |
| ISBN | : |
| Author | : John Cowgill |
| Publisher | : |
| Total Pages | : 0 |
| Release | : 2020 |
| Genre | : |
| ISBN | : |
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.
