Structure, Function and Modulation of Neuronal Voltage-Gated Ion Channels

Examines new research on the role of cholesterol in regulating ion channels and receptors and its effect on health Drawing together and analyzing all the latest research findings, this book explores the role of cholesterol in the regulation of ion channels and receptors, including its pathological effects. It is the first book to comprehensively describe the complex mechanisms by which cholesterol regulates two major classes of membrane proteins. Moreover, it sheds new light on how cholesterol affects essential cellular functions such as the contraction of the heart, propagation of nerve impulses, and regulation of blood pressure and kidney function. Written and edited by leading pioneers in the field, Cholesterol Regulation of Ion Channels and Receptors is divided into three parts: Part I, Cholesterol Regulation of Membrane Properties, introduces the heterogeneity of cholesterol distribution in biological membranes and the physical and biological implications of the formation of cholesterol-rich membrane domains. Part II, Cholesterol Regulation of Ion Channels, examines the mechanisms underlying cholesterol sensitivities of ion channels, including the regulation of ion channels by cholesterol as a boundary lipid. Part III, Cholesterol Regulation of Receptors, explores the latest discoveries concerning how cholesterol regulates distinct types of receptors, including G-protein coupled receptors, LDL and scavenger receptors, and innate immune system receptors. Increased levels of cholesterol represent a major health risk. Understanding cholesterol regulation of ion channels and receptors is essential for facilitating the development of new therapeutic strategies to alleviate the impact of pathological cholesterol conditions. With this book as their guide, readers have access to the most current knowledge in the field.

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.

Presents an integrated view of the expression of bacterial genetic information, genome architecture and function, and bacterial physiology and pathogenesis This book blends information from the very latest research on bacterial chromosome and nucleoid architecture, whole-genome analysis, cell signaling, and gene expression control with well-known gene regulation paradigms from model organisms (including pathogens) to give readers a picture of how information flows from the environment to the gene, modulating its expression and influencing the competitive fitness of the microbe. Structure and Function of the Bacterial Genome explores the governance of the expression of the genes that make a bacterium what it is, and updates the basics of gene expression control with information about transcription promoter structure and function, the role of DNA as a regulatory factor (in addition to its role as a carrier of genetic information), small RNAs, RNAs that sense chemical signals, ribosomes and translation, posttranslational modification of proteins, and protein secretion. It looks at the forces driving the conservation and the evolution of the dynamic genome and offers chapters that cover DNA replication, DNA repair, plasmid biology, recombination, transposition, the roles of repetitive DNA sequences, horizontal gene transfer, the defense of the genome by CRISPR-Cas, restriction enzymes, Argonaute proteins and BREX systems. The book finishes with a chapter that gives an integrated overview of genome structure and function.  Blends knowledge of gene regulatory mechanisms with a consideration of nucleoid structure and dynamics Offers a 'DNA-centric' approach to considering transcription control Views horizontal gene transfer from a gene regulation perspective Assesses the opportunities and limitations of designing synthetic microbes or rewiring existing ones Structure and Function of the Bacterial Genome is an ideal book for graduate and undergraduate students studying microbial cell biology, bacterial pathogenesis, gene regulation, and molecular microbiology. It will also appeal to principal investigators conducting research on these and related topics and researchers in synthetic biology and other arms of biotechnology.

The Novartis Foundation Series is a popular collection of the proceedings from Novartis Foundation Symposia, in which groups of leading scientists from a range of topics across biology, chemistry and medicine assembled to present papers and discuss results. The Novartis Foundation, originally known as the Ciba Foundation, is well known to scientists and clinicians around the world.

This book contains extremely detailed and informative content on structure and function of ligands, receptors, and signalling intermediates plus interactions … the extent of detail and appropriate referencing is impressive. –Microbiology Today, July 2009 «A very well-written book suitable for use as a reference or textbook for an undergraduate subject in cell signalling. For researchers interested in the molecular basis of cell signalling and how aberrant regulation of cell signalling proteins causes diseases, this is an excellent resource of biochemical and structural information.» –Australian Biochemist, August 2009 «From basics to details, this is an elegantly written and carefully edited book. The chapters on cell cycle control and oncogenesis are particularly fascinating and valuable to biomedical research. This is the book to have if you are interested in molecular mechanisms of signal transduction. It is a great introduction to the literature that will be welcomed by students and experts alike.» –Doody's, January 2009 This text is a concise and accessible introduction to the dynamic but complex field of signal transduction. Rather than simply cataloguing all signalling molecules and delineating every known pathway, this book aims to break signalling down into common elements and activities – the ‘nuts and bolts’ of cellular information exchange. With an emphasis on clarity of presentation throughout, the book teaches the basic principles focusing on a mature core of knowledge, providing students with a foundation of learning in this complex and potentially confusing subject. It also addresses the issue of variation in the numbering of key amino acids as well as featuring interaction with RasMol software, and exercises to aid understanding. An accessible introduction to the complex field of cell signalling Interacts with RasMol software – freely downloadable for viewing structures in 3D Includes exercises and clear instructions in the use of RasMol Well illustrated in full colour throughout Structure and Function in Cell Signalling is an invaluable resource to students across a range of life science degree programmes including biochemistry, cell and molecular biology, physiology, biomedicine and oncology. This book provides a clear, accessible introduction to this rapidly expanding field.

Human Oral Mucosa: Development, Structure and Function is a new text that reflects the considerable increase in knowledge of oral mucosa that has occurred in recent years. Our understanding of the structure of oral mucosa is now established at a molecular rather than a tissue or cellular level. This in turn has revealed a level of function that was previously not suspected, including a sophisticated barrier to the penetration of exogenous materials, and the synthesis of specific antimicrobial compounds, representing components of the innate immune system. There is also a growing realization of commonality in structure and function between regions of oral mucosa and the mucosae of the esophagus and vagina. The aim of the present volume is to provide a more sophisticated text on human oral mucosa than presently exists in textbooks and to bring together information that is otherwise to be found in separate, specialist volumes into a comprehensive text. It relates structure at the molecular, cellular and tissue level to function and to clinical behavior. The volume is directed to advanced students and researchers in oral biology, as well as those in allied areas of investigation, such as dermatology, gynecology, internal medicine and pathology.

Although normally thought of as a sex hormone, recent research has highlighted the numerous and significant effects that oestrogen has on the CNS, extending far beyond its important reproductive role. It has been shown that oestrogen acts as a neural growth factor with important influences on the survival, plasticity, regeneration and ageing of the mammalian brain. This exciting book brings together leading clinicians and researchers to discuss oestrogen's basic mechanisms of action, the extrahypothalmic brain regions it affects, and its influence on cognitive functions in animals and humans. Finally, recent research on the role of oestrogens in ageing and dementia, including the significance of oestrogen action in Alzheimer's disease, is discussed. The 15 papers contained in this book, together with the extensive discussion sessions that follow them, reveal much new and exciting work in this area, and identify promising new research directions.

Classical studies of steroid hormones are concerned with their regulation of protein synthesis via the modulation of genomic transcription. But many of the actions of these hormones occur too rapidly to be explained in this manner, particularly their effects on the central nervous system. This text deals with recent discoveries showing that steroids can modulate the activity of some neurotransmitters. It explores the role of GABA as an important regulator of neuronal activity in the central nervous system and its inhibitory action as mediated via the GABA receptor and potentiated by steroids. In addition, the binding of steroids to cell membranes, the components involved and the outcome of such interactions are described. Also discusses possible uses of steroids as anesthetics and anticonvulsants.

Describes experimental methods for investigating the function of pumps, channels and transporters Covers new emerging analytical methods used to study ion transport membrane proteins such as single-molecule spectroscopy Details a wide range of electrophysiological techniques and spectroscopic methods used to analyze the function of ion channels, ion pumps and transporters Covers state-of-the art analytical methods to study ion pumps, channels, and transporters, and where analytical chemistry can make further contributions

A complete guide to the role of high-density lipoproteins (HDL) in new and emerging therapies With high-density lipoproteins (HDL) playing an increasing role in cardiovascular disease prevention, there is a growing need for an in-depth look at HDL and its clinical value. This book summarizes the current state of knowledge in the field, providing for the first time a comprehensive, systematic, stylistically coherent, and up-to-date review of the composition, structure, heterogeneity, metabolism, epidemiology, genetics, and function of HDL. Divided into three main parts, High-Density Lipoproteins first examines normal HDL particles, then describes defective HDL, and finally addresses the therapeutic normalization of subnormal levels and defective biological activities of this lipoprotein class. The book highlights the functional properties of HDL, which are relevant to the pathophysiology of atherosclerosis and thrombosis, and discusses the compositional and metabolic heterogeneity of HDL particles. Readers will come away with a clear understanding of the role of HDL in biological processes, the potential value of functional HDL as a therapeutic target, and how current and emerging therapies are poised to influence the treatment of heart disease in the future.