Download or read book The Mechanism of Action of External Protons on HERG Potassium Channels written by Yu Shi and published by . This book was released on 2018 with total page 178 pages. Available in PDF, EPUB and Kindle. Book excerpt: Myocardial ischemia occurs when there is a reduction of blood flow to the heart due to blockage of an artery, causing inefficient delivery of oxygen and nutrients to the heart muscle. Acidosis is one of the major consequences during myocardial ischemia and affects a wide array of ion channels in the heart that may predispose individuals to cardiac arrhythmia. The human ether-à-go-go (hERG) related gene encodes the potassium channel that conducts the IKr current, which is responsible for the repolarization phase of the cardiac action potential and is particularly sensitive to external acidosis. External acidosis had been well observed to reduce hERG channel overall conductance, right-shift the voltage-dependence of activation, and accelerate deactivation rate, all of which lead to a loss-of-function effect on the hERG channels. We hypothesized that this can prolong action potential duration, increase susceptibility of individuals to long QT syndrome and reduce the protective current against premature ectopic beat. My first study aimed to determine the site and mechanism for the right-shift in the voltage-dependence of activation. I found that external protons disrupt stable interactions formed by the cation binding pocket, compose of three acidic residues: D456, D460 in S2, and D509 in S3, with positive charges in S4 to destabilize the activated voltage sensor. My second study aims to determine the site and mechanism for the acceleration of deactivation induced by external protons. Using voltage-clamp fluorimetry and gating current measurement with long duration protocols to measure voltage sensor mode-shift, we determined that external protons reduced the voltage sensor mode-shift by right shifting the voltage-dependence of deactivation suggesting that the relaxed conformation of the voltage sensor is destabilized and that D509 is a critical protonation site. In my last study, I used zebrafish heart as a translational model, with the optical mapping technique to investigate the effect of external protons on the overall cardiac action potential. We discovered that at low pH, the cardiac action potential is significantly prolonged, triangulation is increased, and the electrical restitution curve is flattened, which are all predictors for arrhythmogenicity.
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 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 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.
Download or read book Protein Blood Group Antigens of the Human Red Cell written by Peter Agre and published by . This book was released on 1992 with total page 296 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Tactics in Contemporary Drug Design written by Nicholas A. Meanwell and published by Springer. This book was released on 2014-12-08 with total page 400 pages. Available in PDF, EPUB and Kindle. Book excerpt: Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.
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 Nutritional and Metabolic Diseases New Insights for the Healthcare Professional 2013 Edition written by and published by ScholarlyEditions. This book was released on 2013-07-22 with total page 356 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nutritional and Metabolic Diseases: New Insights for the Healthcare Professional: 2013 Edition is a ScholarlyEditions™ book that delivers timely, authoritative, and comprehensive information about Diagnosis and Screening. The editors have built Nutritional and Metabolic Diseases: New Insights for the Healthcare Professional: 2013 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Diagnosis and Screening in this book to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Nutritional and Metabolic Diseases: New Insights for the Healthcare Professional: 2013 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.
Download or read book Novel Chemical Tools to Study Ion Channel Biology written by Christopher Ahern and published by Springer. This book was released on 2015-09-17 with total page 159 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume describes chemical approaches to assess ion channel structure, function and pharmacology. Topics discussed include the use of engineered ionizable side chains to obtain information on permeation pathways and the local environment; the modification of engineered cysteine side chains, including cysteine scanning mutagenesis and the attachment of fluorescent probes and bio-reactive tethers; and the nascent use of genetic code expansion, evaluating its applications to ion channel and membrane proteins. This comprehensive text provides multifaceted perspectives on the great diversity of state-of-the-art methods which take advantage of the ever-expanding chemical toolbox to study ion channel biology. Capturing the contributions and innovations of renowned laboratory researchers in transmembrane protein study for the first time, this book is comprehensive in scope. It covers a wide array of experimental approaches: photochemistry, novel biological tools, and innovative spectroscopy, all combined with traditional techniques of electrophysiology and molecular biology. Novel Chemical Tools to Study Ion Channel Biology, part of the bestselling Advances in Experimental Medicine and Biology series is ideal for researchers and advanced students interested in biochemistry, biophysics, fluorometry, electrophysiology, and chemical biology. .
Download or read book Potassium Channels written by Simone Furini and published by Springer Nature. This book was released on with total page 298 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Molecular Basis of Cardiovascular Disease written by Kenneth R. Chien and published by . This book was released on 2004 with total page 760 pages. Available in PDF, EPUB and Kindle. Book excerpt: The 2nd Edition of this heralded companion to Braunwald's Heart Disease explores the molecular mechanisms of cardiology and the scientific advances that are changing the practice of cardiology today. International experts discuss the role of genetics in cardiovascular disease the molecular basis of ischemic disease, thrombosis and hypertension genetic mapping approaches to inherited disorders biologically targeted agents for hypertension and heart failure and much more. Abundant figures and tables illustrate key concepts. Addresses most common cardiovascular problems from a molecular standpoint. Explores developing treatments for cardiovascular problems based on genetics. Provides references to Braunwald's Heart Disease, 6th Edition Examines today's cutting edge advances in molecular cardiology and the future of gene therapy, Examines the implications of cellular cholesterol metabolism in health and disease. . Delivers up-to-date information on understanding the origin of inherited disease.
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 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.
Download or read book Ion Channel Diseases written by and published by Academic Press. This book was released on 2011-09-06 with total page 168 pages. Available in PDF, EPUB and Kindle. Book excerpt: Ion channel dysfunction in humans leads to impairment of the excitable processes necessary for the normal function of several tissues, such as muscle and brain. It follows that an increasing number of human diseases have been associated with malfunctioning ion channels, many of which have a genetic component. This volume of Advances in Genetics presents a broad and comprehensive overview of the inherited channelopathies in humans, including clinical, genetic and molecular aspects of these conditions. Keeping true to the scope of the serial, novel genomic and modeling research approaches and a review of potential therapeutic approaches for each of these conditions are also incorporated.
Download or read book Sensory Nerves written by Brendan J. Canning and published by Springer Science & Business Media. This book was released on 2009-08-05 with total page 623 pages. Available in PDF, EPUB and Kindle. Book excerpt: The intention of this book is to provide a comprehensive and contemporary review of the biology of sensory nerves. The book is unique, as it comprehensively covers the role of sensory nerves across many therapeutic areas.
Download or read book The Anaesthesia Science Viva Book written by Simon Bricker and published by Cambridge University Press. This book was released on 2005 with total page 356 pages. Available in PDF, EPUB and Kindle. Book excerpt: The definitive guide to this part of the FRCA exam.
Download or read book Acquired Long QT Syndrome written by A. John Camm and published by John Wiley & Sons. This book was released on 2008-04-15 with total page 208 pages. Available in PDF, EPUB and Kindle. Book excerpt: In recent years there has been considerable interest in the diagnosis and understanding of ventricular repolarisation, particularly the QT interval prolongation and abnormal T and T/U wave morphology associated with torsades de pointes. Advances in ion channel cloning have greatly improved our understanding of the role of ionic channels in mediating cardiac repolarisation. Unfortunately, it is increasingly recognised that a number of drugs, both those associated with altering repolarisation, and others for non-cardiac conditions can increase the propensity for polymorphic ventricular tachycardia, syncope and even ventricular fibrillation and sudden death. In this volume, arrhythmia specialists from St. George’s Hospital Medical School, London discuss the mechanisms behind QT prolongation and torsades de pointes. They focus particularly on the risk of individual cardiac and non-cardiac drugs in provoking long QT syndrome, providing a comprehensive review which will be useful for all electrophysiologists treating polymorphic ventricular tachycardias, and will expose important regulatory issues for pharmaceutical authorities and for the wider medical community.
