Ion Channel Localization


Book Description

Since the pioneering discoveries of Hodgkin, Huxley, and Katz, it has been clear that specific ion conductance pathways underlie electrical act- ity. Over the ensuing 50 years, there has been ever increasing, and occasi- ally explosive, changes in the scope of efforts to understand ion channel behavior. The introduction of patch clamp technology by Erwin Neher and Bert Sakmann about 20 years ago led to the realization of the great variety of novel ion channel species, and the subsequent revolution in cl- ing has revealed an even greater diversity of the underlying molecular entities. Today, advances in the study of ion channel structure and function c- tinue at a high pace, from angstrom resolution imaging of crystallized ch- nels to their genetic manipulations in animals. In this regard, the field is a balanced one that inquires not only what ion channel entities are there, or how they operate, but also where are these molecular electronic switches? However, this balance is not particularly well presented to the general sci- tific audience or to specialists in the field. There are plenty of wonderful and useful books and monographs, as well as conferences and meetings on v- tually every aspect of ion channel structure and function. However, we are unaware that the channel localization theme has been considered in a u- fied forum.




Handbook of Ion Channels


Book Description

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




Ion Channels


Book Description

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.




Textbook of Ion Channels Volume I


Book Description

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.




Ion Channels


Book Description

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.







Ion Channels


Book Description

In the past few years, the scientific community has witnessed significant progress in the study of ion channels. Technological advancement in biophysics, molecular biology, and immunology has been greatly ac celerated, making it possible to conduct experiments which were deemed very difficult if not impossible in the past. For example, patch-clamp techniques can now be used to measure ionic currents generated by almost every type of cell, thereby allowing us to analyze whole-cell and single channel events. It is now possible to incorporate purified ion channel components into lipid bilayers to reconstitute an "excitable membrane." Gene cloning and monoclonal antibody techniques provide us with new approaches to the study of the molecular structure of ion channels. A variety of chemicals have now been found to interact with ion channels. One of the classical examples is represented by tetrodotoxin, a puffer fish poison, which was shown in the early 1960s to block the voltage-activated sodium channel in a highly specific and potent manner.




Ion Channel Localization and Determinants of Localization


Book Description

"Ion channels constitute a class of proteins that is ultimately responsible for generating and coordinating electrical signals passing through the brain and heart. In order for ion channels to fulfill these roles a number of coordinated events must ensue at the protein level. Newly translated polypeptides entering the endoplasmic reticulum (ER) must be correctly processed and folded in order to exit. In the case of voltage-dependent ion channels, the channel alpha subunits, which form the channel pore, oligomerize with like (or unlike) alpha subunits and/or auxiliary (beta) subunits, depending on the channel type. Further posttranslational modifications take place within the Golgi apparatus before the channels embark for their final destination. Once there, or prior to their arrival, they interact with cytoskeletal elements that serve to anchor the channel in place and tether accessory elements involved in ion channel modulation and signaling. Here, I have investigated the role of N-linked glycosylation in the surface membrane expression of a K+ channel, human ether-a-go-go related gene (HERG), mutation of which can give rise to the cardiac disease long QT. Pharmacological and site-directed mutagenesis reveal that N-linked glycosylation is required for proper channel processing and cell surface expression of HERG as determined through immunoblot, immunocytochemical and electrophysiological analysis. Removal of glycosylation leads to an intracellular retention of HERG. Furthermore, I have examined the subcellular localization of the Na+/H+ exchanger (NHE1 isoform) in cardiomyocytes using immunocytochemical techniques and found that it exhibits a restricted subcellular localization at the intercalated disc. Along the same line, using the yeast two-hybrid screening technique, I have identified an actin-binding protein, filamin, that directly interacts with and plays a role in the subcellular localization of a prominent heart and brain K + channel, Kv4.2." --




Trafficking of Cardiac Ion Channels


Book Description

Protein sorting and trafficking are regulated by well-conserved mechanisms. These allow a distinctive set of resident proteins to be present in the correct subcellular organelle, which is required for proper cell functioning. Voltage-gated ion channels, as responsible for cardiomyocyte action potential, must be properly localized. They participate in cell excitability and electrical coupling, ensuring uninterrupted and rhythmic heart beating. Ion channel complexes comprise one or more pore-forming α subunits, associated β subunits, and additional proteins. Channel localization and function are regulated by the β subunits and associated proteins, such as cytoskeletal elements, cell-adhesion molecules, and adaptors. These influence protein targeting, anchoring, and retention in specific surface domains along the cardiomyocyte sarcolemma, such as intercalated discs, T-tubules, or the lateral membrane. Alterations in ion channel trafficking are the cause of channelopathies associated with inherited arrhythmias leading to sudden death. An outstanding question is how these molecular alterations lead to disease. In this volume, scientists share their vision to understand how cardiac ion channel trafficking is regulated and how it may become altered, leading to channelopathies that often turn into deadly arrhythmias. Data generated can be translated to a clinical context, hopefully turning into approaches to help prevention and treatment, which is of utmost importance, both medically and socially.




Ion Channel Regulation


Book Description

Volume 33 reviews the current understanding of ion channel regulation by signal transduction pathways. Ion channels are no longer viewed simply as the voltage-gated resistors of biophysicists or the ligand-gated receptors of biochemists. They have been transformed during the past 20 years into signaling proteins that regulate every aspect of cell physiology. In addition to the voltage-gated channels, which provide the ionic currents to generate and spread neuronal activity, and the calcium ions to trigger synaptic transmission, hormonal secretion, and muscle contraction, new gene families of ion channel proteins regulate cell migration, cell cycle progression, apoptosis, and gene transcription, as well as electrical excitability. Even the genome of the lowly roundworm Caenorhabditis elegans encodes almost 100 distinct genes for potassium-selective channels alone. Most of these new channel proteins are insensitive to membrane potential, yet in humans, mutations in these genes disrupt development and increase individual susceptibility to debilitating and lethal diseases.How do cells regulate the activity of these channels? How might we restore their normal function? In Ion Channel Regulation, many of the experts who pioneered these discoveries provide detailed summaries of our current understanding of the molecular mechanisms that control ion channel activity. Reviews brain functioning at the fundamental, molecular level Describes key systems that control signaling between and within cells Explains how channels are used to stimulate growth and changes to activity of the nucleus and genome