Ion Channel Drug Discovery

Ion Channel Drug Discovery

Author: Brian Cox

Publisher: Royal Society of Chemistry

Published: 2014-09-03

Total Pages: 385

ISBN-13: 1849735085

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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.


Ion Channels and Disease

Ion Channels and Disease

Author: Frances M. Ashcroft

Publisher: Academic Press

Published: 1999-10-20

Total Pages: 505

ISBN-13: 0080535216

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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


The Endothelium

The Endothelium

Author: Michel Félétou

Publisher: Morgan & Claypool Publishers

Published: 2011

Total Pages: 309

ISBN-13: 1615041230

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The endothelium, a monolayer of endothelial cells, constitutes the inner cellular lining of the blood vessels (arteries, veins and capillaries) and the lymphatic system, and therefore is in direct contact with the blood/lymph and the circulating cells. The endothelium is a major player in the control of blood fluidity, platelet aggregation and vascular tone, a major actor in the regulation of immunology, inflammation and angiogenesis, and an important metabolizing and an endocrine organ. Endothelial cells controls vascular tone, and thereby blood flow, by synthesizing and releasing relaxing and contracting factors such as nitric oxide, metabolites of arachidonic acid via the cyclooxygenases, lipoxygenases and cytochrome P450 pathways, various peptides (endothelin, urotensin, CNP, adrenomedullin, etc.), adenosine, purines, reactive oxygen species and so on. Additionally, endothelial ectoenzymes are required steps in the generation of vasoactive hormones such as angiotensin II. An endothelial dysfunction linked to an imbalance in the synthesis and/or the release of these various endothelial factors may explain the initiation of cardiovascular pathologies (from hypertension to atherosclerosis) or their development and perpetuation. Table of Contents: Introduction / Multiple Functions of the Endothelial Cells / Calcium Signaling in Vascular Cells and Cell-to-Cell Communications / Endothelium-Dependent Regulation of Vascular Tone / Conclusion / References


Biomimetic Membranes for Sensor and Separation Applications

Biomimetic Membranes for Sensor and Separation Applications

Author: Claus Hélix-Nielsen

Publisher: Springer Science & Business Media

Published: 2012-01-02

Total Pages: 303

ISBN-13: 9400721846

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This book addresses the possibilities and challenges in mimicking biological membranes and creating membrane-based sensor and separation devices. Recent advances in developing biomimetic membranes for technological applications will be presented with focus on the use of integral membrane protein mediated transport for sensing and separation. It describes the fundamentals of biosensing as well as separation and shows how the two processes are working in a cooperative manner in biological systems. Biomimetics is a truly cross-disciplinary approach and this is exemplified using the process of forward osmosis will be presented as an illustration of how advances in membrane technology may be directly stimulated by an increased understanding of biological membrane transport. In the development of a biomimetic sensor/separation technology, both channels (ion and water channels) and carriers (transporters) are important. An ideal sensor/separation device requires the supporting biomimetic matrix to be virtually impermeable to anything but the solute in question. In practice, however, a biomimetic support matrix will generally have finite permeabilities to water, electrolytes, and non-electrolytes. These non-protein mediated membrane transport contributions will be presented and the implications for biomimetic device construction will be discussed. New developments in our understanding of the reciprocal coupling between the material properties of the biomimetic matrix and the embedded proteins will be presented and strategies for inducing biomimetic matrix stability will be discussed. Once reconstituted in its final host biomimetic matrix the protein stability also needs to be maintained and controlled. Beta-barrel proteins exemplified by the E. Coli outer membrane channels or small peptides are inherently more stable than alpha-helical bundle proteins which may require additional stabilizing modifications. The challenges associated with insertion and stabilization of alpha-helical bundle proteins including many carriers and ligand and voltage gated ion (and water) channels will be discussed and exemplified using the aquaporin protein. Many biomimetic membrane applications require that the final device can be used in the macroscopic realm. Thus a biomimetic separation device must have the ability to process hundred of liters of permeate in hours – effectively demanding square-meter size membranes. Scalability is a general issue for all nano-inspired technology developments and will be addressed here in the context biomimetic membrane array fabrication. Finally a robust working biomimetic device based on membrane transport must be encapsulated and protected yet allowing massive transport though the encapsulation material. This challenge will be discussed using microfluidic design strategies as examples of how to use microfluidic systems to create and encapsulate biomimetic membranes. The book provides an overview of what is known in the field, where additional research is needed, and where the field is heading.


Biochemistry of Smooth Muscle Contraction

Biochemistry of Smooth Muscle Contraction

Author: Michael Barany

Publisher: Elsevier

Published: 1996-01-04

Total Pages: 455

ISBN-13: 0080527892

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This valuable resource provides a systematic account of the biochemistry of smooth muscle contraction. As a comprehensive guide to this rapidly growing area of research, it covers the structure and characteristic properties of contractile and regulatory proteins, with special emphasis on their predicted function in the live muscle. Also included in this book are intermediate filament proteins, and desmin and vimentin, whose function in smooth muscle is unknown; and several enzymes involved in the phosphorylation-dephosphorylation of contractile and other proteins.


Magnesium in the Central Nervous System

Magnesium in the Central Nervous System

Author: Robert Vink

Publisher: University of Adelaide Press

Published: 2011

Total Pages: 354

ISBN-13: 0987073052

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The brain is the most complex organ in our body. Indeed, it is perhaps the most complex structure we have ever encountered in nature. Both structurally and functionally, there are many peculiarities that differentiate the brain from all other organs. The brain is our connection to the world around us and by governing nervous system and higher function, any disturbance induces severe neurological and psychiatric disorders that can have a devastating effect on quality of life. Our understanding of the physiology and biochemistry of the brain has improved dramatically in the last two decades. In particular, the critical role of cations, including magnesium, has become evident, even if incompletely understood at a mechanistic level. The exact role and regulation of magnesium, in particular, remains elusive, largely because intracellular levels are so difficult to routinely quantify. Nonetheless, the importance of magnesium to normal central nervous system activity is self-evident given the complicated homeostatic mechanisms that maintain the concentration of this cation within strict limits essential for normal physiology and metabolism. There is also considerable accumulating evidence to suggest alterations to some brain functions in both normal and pathological conditions may be linked to alterations in local magnesium concentration. This book, containing chapters written by some of the foremost experts in the field of magnesium research, brings together the latest in experimental and clinical magnesium research as it relates to the central nervous system. It offers a complete and updated view of magnesiums involvement in central nervous system function and in so doing, brings together two main pillars of contemporary neuroscience research, namely providing an explanation for the molecular mechanisms involved in brain function, and emphasizing the connections between the molecular changes and behavior. It is the untiring efforts of those magnesium researchers who have dedicated their lives to unraveling the mysteries of magnesiums role in biological systems that has inspired the collation of this volume of work.


Mechanosensitive Ion Channels, Part B

Mechanosensitive Ion Channels, Part B

Author:

Publisher: Elsevier

Published: 2011-09-21

Total Pages: 610

ISBN-13: 0080494404

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Current Topics in Membranes provides a systematic, comprehensive, and rigorous approach to specific topics relevant to the study of cellular membranes. Each volume is a guest edited compendium of membrane biology. This series has been a mainstay for practicing scientists and students interested in this critical field of biology. Articles covered in the volume include ENaC Proteins in Vascular Smooth Muscle Mechanotransduction; Regulation of the Mechano-Gated K2P Channel TREK-1 by Membrane Phospholipids; MechanoTRPs and TRPA1; TRPC; The Cytoskeletal Connection to Ion Channels as a Potential Mechanosensory Mechanism. Lessons From Polycystin-2 (TRPP2); Lipid Stress at Play: Mechanosensitivity of Voltage-Gated Channels; Hair Cell Mechanotransduction: The Dynamic Interplay between Structure and Function; Pharmacology of Hair Cell MS Channels; Hair Cell Mechanotransduction; Models of Hair Cell Mechanotrasduction; Touch; Mechanosensitive Ion Channels in Dystrophic Muscle; Mechanotransduction in Endothelial Cells;MS Channels in Tumor Cell Migration; Mechanosensitive Channels in Regulating Smooth Muscle Contraction in the GI; Mechanosensitive Ion Channels in Blood-Pressure-Sensing Baroreceptor Neurons.


Cellular and Molecular Neurophysiology

Cellular and Molecular Neurophysiology

Author: Constance Hammond

Publisher: Academic Press

Published: 2014-12-30

Total Pages: 444

ISBN-13: 0123973228

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Cellular and Molecular Neurophysiology, Fourth Edition, is the only up-to-date textbook on the market that focuses on the molecular and cellular physiology of neurons and synapses. Hypothesis-driven rather than a dry presentation of the facts, the book promotes a real understanding of the function of nerve cells that is useful for practicing neurophysiologists and students in a graduate-level course on the topic alike. This new edition explains the molecular properties and functions of excitable cells in detail and teaches students how to construct and conduct intelligent research experiments. The content is firmly based on numerous experiments performed by top experts in the field This book will be a useful resource for neurophysiologists, neurobiologists, neurologists, and students taking graduate-level courses on neurophysiology. - 70% new or updated material in full color throughout, with more than 350 carefully selected and constructed illustrations - Fifteen appendices describing neurobiological techniques are interspersed in the text


Ion Channel Pharmacology

Ion Channel Pharmacology

Author: Bernat Soria

Publisher:

Published: 1998

Total Pages: 498

ISBN-13:

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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.