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.

Modern applications of electrophysiologica techniques; Expression of ion channels; Expression of ion channels in Xenopus oocytes; Expression of ion channels using other systems; Reconstruction of ion channels in lipid bilayers; Recording of ion channels of cellular organelles and miroorganisms; Data storage and analysis.

Ion Channels, Part C, Volume 653 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 Nonsense suppression in ion channels, Engineering Ion Channels Using Protein Trans-splicing, Probing Ion Channel Neighborhoods Using APEX, STX based probes for NaVs, ANAP: a versatile, fluorescent probe of ion channel gating and regulation, High Throughput Screens for Small Molecule Ion Channel Modulators, Using toxins to study ion channels, Re/de-constructing ubiquitin regulation of ion channels, Tethered Peptide Toxins for Ion Channels, Voltage-Sensing Phosphatase Molecular Engineering, and more. Additional chapters cover Engineering excitable cells, Stretch and Poke Stimulation of Mechanically-Activated Ion Channels, Optical Control of STIM Channels, High Throughput Electrophysiological Evaluation of Mutant Ion Channels, Evaluating BEST1 Mutations in RPE Stem Cells, Long Read Transcript Profiling of Ion Channel Splice Variants, Permeation of Connexin Channels, Ratiometric pH indicator for melanosomes and lysosomes, and Ion channels in the epithelial cells of the choroid plexus. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Methods in Enzymology series

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 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.

Receptor and Ion Channel Detection in the Brain provides state-of-the-art and up-to-date methodological information on molecular, neuroanatomical and functional techniques that are currently used to study neurotransmitter receptors and ion channels in the brain. The chapters have been contributed by world-wide recognized neuroscientists who explain in an easy and detailed way well established and tested protocols embracing molecular, cellular, subcellular, anatomical and electrophysiological aspects of the brain. This comprehensive and practical manual is presented in a simple, step-by-step manner for laboratory use, and also offers unambiguous detail and key implementation advice that proves essential for successful results and facilitate choosing the best method for the target proteins under study. This work serves as a useful guide for young researchers and students in training as well as for neurologists and established scientists who wish to extend their repertoire of techniques.

Ion channel drug discovery is a rapidly evolving field fuelled by recent, but significant, advances in our understanding of ion channel function combined with enabling technologies such as automated electrophysiology. The resurgent interest in this target class by both pharmaceutical and academic scientists was clearly highlighted by the over-subscribed RSC/BPS 'Ion Channels as Therapeutic Targets' symposium in February 2009. This book builds on the platform created by that meeting, covering themes including advances in screening technology, ion channel structure and modelling and up-to-date case histories of the discovery of modulators of a range of channels, both voltage-gated and non-voltage-gated channels. The editors have built an extensive network of contacts in the field through their first-hand scientific experience, collaborations and conference participation and the organisation of the meeting at Novartis, Horsham, increased the network enabling the editors to draw on the experience of eminent researchers in the field. Interest and investment in ion channel modulation in both industrial and academic settings continues to grow as new therapeutic opportunities are identified and realised for ion channel modulation. This book provides a reference text by covering a combination of recent advances in the field, from technological and medicinal chemistry perspectives, as well as providing an introduction to the new 'ion channel drug discoverer'. The book has contributions from highly respected academic researchers, industrial researchers at the cutting edge of drug discovery and experts in enabling technology. This combination provides a complete picture of the field of interest to a wide range of readers.