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Author : James Joseph Fleming
Publisher :
ISBN 13 :
Total Pages : 744 pages
Book Rating : 4.F/5 ( download)
Download or read book Using Small Molecules to Investigate the Voltage-gated Sodium Channel written by James Joseph Fleming and published by . This book was released on 2006 with total page 744 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Author : Justin David Litchfield
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (649 download)
Download or read book Using Synthetic Small Molecules to Probe the Structure and Function of Voltage-gated Ion Channels written by Justin David Litchfield and published by . This book was released on 2010 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Several methods of examining the structure and function of voltage-gated ion channels are described. The first part of this work involves synthetic small molecules based on the structure of (+)-saxitoxin, a marine neurotoxin. (+)-saxitoxin interacts with the pore of the voltage-gated sodium (NaV) channel to prevent the passage of ions. A scaffold was designed to be modular, synthetically facile, and contain the functionality that had been implicated in the previous literature. Several members of this family of molecules were produced, and they were assayed for occlusion of sodium current (INa). The second part of this work examines the gating kinetics of voltage-gated potassium (KV) channels. 6-bromo-mercaptotryptamine (BrMT) is a marine neurotoxin that has been shown to alter the gating kinetics of KV channels. Specifically, BrMT affects the early, typically independent steps of KV gating by stabilizing the resting state of some number of the subunits. A family of small molecules was designed and synthesized that would examine the functional effects of different parts of the BrMT molecule. BrMT is a dimer containing three key functional groups: a halogenated indole, a pendant ethyl-amine, and a disulfide linker. Variance at all these positions was examined, and each had different effects. Notably, one of the variants, in which the disulfide linker was substituted for an oxy-bismethyl ether linker, affects KV gating in a different way from BrMT. Alternate models of gating in the presence of this novel analog are discussed.
Author : Peter C. Ruben
Publisher : Springer Science & Business Media
ISBN 13 : 3642415881
Total Pages : 328 pages
Book Rating : 4.6/5 (424 download)
Download or read book Voltage Gated Sodium Channels written by Peter C. Ruben and published by Springer Science & Business Media. This book was released on 2014-04-15 with total page 328 pages. Available in PDF, EPUB and Kindle. Book excerpt: A number of techniques to study ion channels have been developed since the electrical basis of excitability was first discovered. Ion channel biophysicists have at their disposal a rich and ever-growing array of instruments and reagents to explore the biophysical and structural basis of sodium channel behavior. Armed with these tools, researchers have made increasingly dramatic discoveries about sodium channels, culminating most recently in crystal structures of voltage-gated sodium channels from bacteria. These structures, along with those from other channels, give unprecedented insight into the structural basis of sodium channel function. This volume of the Handbook of Experimental Pharmacology will explore sodium channels from the perspectives of their biophysical behavior, their structure, the drugs and toxins with which they are known to interact, acquired and inherited diseases that affect sodium channels and the techniques with which their biophysical and structural properties are studied.
Author : Juliusz Ashot Kozak
Publisher : CRC Press
ISBN 13 : 149875273X
Total Pages : 343 pages
Book Rating : 4.4/5 (987 download)
Download or read book Calcium Entry Channels in Non-Excitable Cells written by Juliusz Ashot Kozak and published by CRC Press. This book was released on 2017-07-14 with total page 343 pages. Available in PDF, EPUB and Kindle. Book excerpt: Calcium Entry Channels in Non-Excitable Cells focuses on methods of investigating the structure and function of non-voltage gated calcium channels. Each chapter presents important discoveries in calcium entry pathways, specifically dealing with the molecular identification of store-operated calcium channels which were reviewed by earlier volumes in the Methods in Signal Transduction series. Crystallographic and pharmacological approaches to the study of calcium channels of epithelial cells are also discussed. Calcium ion is a messenger in most cell types. Whereas voltage gated calcium channels have been studied extensively, the non-voltage gated calcium entry channel genes have only been identified relatively recently. The book will fill this important niche.
Author : Timothy Michael Gale MacKenzie
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (17 download)
Download or read book A Synthetic Batrachotoxin Derivative as a Novel Molecular Probe to Study Slow Inactivation in Voltage-gated Sodium Channels written by Timothy Michael Gale MacKenzie and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Voltage-gated sodium channels (NaVs) are obligatory transmembrane proteins responsible for electrical signaling in biology. By transitioning between different conformational states, NaVs initiate the rising phase of the action potential. A large array of neurotoxins target specific conformational states of the channel or disrupt transitions between them. Among the most powerful of these pharmacological tools is batrachotoxin (BTX), the active ingredient in poison-tipped darts used by the indigenous people of Colombia. Every measurable aspect of channel function is disrupted when this potent small molecule binds in the NaV central pore. Using de novo synthesis, we sought to perform structure-activity relationship (SAR) studies to uncover the molecular underpinnings of the action of this potent toxin. SAR studies focused on derivatizing the C20-ester of BTX. Synthetic toxin analogues were characterized using whole-cell voltage clamp electrophysiology. Using this technique, the efficacy of BTX against a recombinantly expressed single channel isoform was measured for the first time. The ester derivatives show comparable ability to the natural product in their ability to hyperpolarize NaV activation potential, indicating changes to this region of the molecule are tolerated. A BTX derivative having a conformationally flexible ester, BTX-yne, uniquely alters NaV inactivation. With the exception of BTX-yne, BTX and all synthetic ester derivatives completely eliminate both fast and slow inactivation, distinct mechanisms that regulate NaV availability. In contrast, BTX-yne selectively eliminates fast inactivation while allowing channels to undergo slow inactivation. Electrophysiology experiments with rNaV1.4 and a prokaryotic sodium channel, NaVAe, were performed to fully characterize the behavior of this novel pharmacological tool compound. A novel sodium channel mutant, rNaV1.4 A438K, that is incapable of fast inactivation was characterized. The behavior of unmodified A438K resembles that of wild-type channels modified by BTX-yne, demonstrating that slow inactivation can be studied without the influence of fast inactivation with small molecules and mutant NaVs. The experiments in this thesis lay the groundwork for future work to understand the molecular elements underlying the dynamic conformational rearrangements that underlie channel gating.
Author :
Publisher :
ISBN 13 : 9780815332183
Total Pages : 0 pages
Book Rating : 4.3/5 (321 download)
Download or read book Molecular Biology of the Cell written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Author : Mohamed Chahine
Publisher : Springer
ISBN 13 : 3319902849
Total Pages : 448 pages
Book Rating : 4.3/5 (199 download)
Download or read book Voltage-gated Sodium Channels: Structure, Function and Channelopathies written by Mohamed Chahine and published by Springer. This book was released on 2018-06-04 with total page 448 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a timely state-of-the-art overview of voltage-gated sodium channels, their structure-function, their pharmacology and related diseases. Among the topics discussed are the structural basis of Na+ channel function, methodological advances in the study of Na+ channels, their pathophysiology and drugs and toxins interactions with these channels and their associated channelopathies.
Author : David J. Triggle
Publisher : John Wiley & Sons
ISBN 13 : 3527607749
Total Pages : 492 pages
Book Rating : 4.5/5 (276 download)
Download or read book Voltage-Gated Ion Channels as Drug Targets written by David J. Triggle and published by John Wiley & Sons. This book was released on 2006-08-21 with total page 492 pages. Available in PDF, EPUB and Kindle. Book excerpt: Edited by the most prominent person in the field and top researchers at US pharmaceutical companies, this is a unique resource for drug developers and physiologists seeking a molecular-level understanding of ion channel pharmacology. After an introduction to the topic, the authors evaluate the structure and function of ion channels, as well as related drug interaction. A section on assay technologies is followed by a section each on calcium, sodium and potassium channels. Further chapters cover genetic and acquired channelopathies, before the book closes with a look at safety issues in ion channel drug development. For medicinal and pharmaceutical chemists, biochemists, molecular biologists and those working in the pharmaceutical industry.
Author : Brian Cox
Publisher : Royal Society of Chemistry
ISBN 13 : 1849735085
Total Pages : 385 pages
Book Rating : 4.8/5 (497 download)
Download or read book Ion Channel Drug Discovery written by Brian Cox and published by Royal Society of Chemistry. This book was released on 2014-09-03 with total page 385 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Author : Jie Zheng
Publisher : CRC Press
ISBN 13 : 1466551429
Total Pages : 682 pages
Book Rating : 4.4/5 (665 download)
Download or read book Handbook of Ion Channels written by Jie Zheng and published by CRC Press. This book was released on 2015-02-25 with total page 682 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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
Author : Fatima Shad Kaneez
Publisher : BoD – Books on Demand
ISBN 13 : 1789842271
Total Pages : 204 pages
Book Rating : 4.7/5 (898 download)
Download or read book Ion Channels in Health and Sickness written by Fatima Shad Kaneez and published by BoD – Books on Demand. This book was released on 2018-10-10 with total page 204 pages. Available in PDF, EPUB and Kindle. Book excerpt: Ion channels are proteins that make pores in the membranes of excitable cells present both in the brain and the body. These cells are not only responsible for converting chemical and mechanical stimuli into the electrical signals but are also liable for monitoring vital functions. All our activities, from the blinking of our eyes to the beating of our heart and all our senses from smell to sight, touch, taste and hearing are regulated by the ion channels. This book will take us on an expedition describing the role of ion channels in congenital and acquired diseases and the challenges and limitations scientist are facing in the development of drugs targeting these membrane proteins.
Author : Gustavo H. Vazquez
Publisher : Academic Press
ISBN 13 : 0128210346
Total Pages : 170 pages
Book Rating : 4.1/5 (282 download)
Download or read book Ketamine for Treatment-Resistant Depression written by Gustavo H. Vazquez and published by Academic Press. This book was released on 2020-09-16 with total page 170 pages. Available in PDF, EPUB and Kindle. Book excerpt: Ketamine for Treatment-Resistant Depression: Neurobiology and Applications provides a simple, evidence-based overview for neuropsychiatrists and translational researchers on this medication, its mechanisms of actions, eligibility of patients for treatment, and the preparation and implementation of ketamine clinics. - Provides efficacy research on ketamine as a treatment for depression - Identifies best practices for clinical use, both long-term and acute - Discusses the molecular mechanisms and neurobiology of action
Author :
Publisher : Academic Press
ISBN 13 : 012809253X
Total Pages : 680 pages
Book Rating : 4.1/5 (28 download)
Download or read book Na Channels from Phyla to Function written by and published by Academic Press. This book was released on 2016-08-29 with total page 680 pages. Available in PDF, EPUB and Kindle. Book excerpt: Na Channels from Phyla to Function, the latest volume in the Current Topics in Membranes series, is targeted toward scientists and researchers in biochemistry and molecular and cellular biology, providing the necessary membrane research to assist them in discovering the current state of a particular field and in learning where that field is heading. This volume offers an up-to-date presentation of the current knowledge in the field of Na Channels. Written by leading experts in the field of Na Channels Contains original material, both textual and illustrative, that make it a very relevant reference Presented in a very comprehensive manner Both researchers in the field and general readers will find this book relevant and up-to-date with regard to its information
Author : Frances M. Ashcroft
Publisher : Academic Press
ISBN 13 : 0080535216
Total Pages : 505 pages
Book Rating : 4.0/5 (85 download)
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
Author : F. Lehmann-Horn
Publisher : Elsevier
ISBN 13 : 0080528856
Total Pages : 383 pages
Book Rating : 4.0/5 (85 download)
Download or read book Channelopathies written by F. Lehmann-Horn and published by Elsevier. This book was released on 2000-11-16 with total page 383 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book describes human hereditary ion channel diseases of voltage- and ligand-gated ion channels covering the diverse fields of medicine myology, neurology, cardiology, and nephrology requiring a wide and interdisciplinary readership. Interesting parallels in pathogenetic mechanisms of disease are especially emphasized to interest even highly specialized readers in entities outside of their fields. Each author has written an objective overview of his or her particular subject in a way that should allow the reader within a short period of time to obtain a comprehensive picture of the present state of art.
Author : Bertil Hille
Publisher : Sinauer Associates, Incorporated
ISBN 13 :
Total Pages : 638 pages
Book Rating : 4.3/5 (91 download)
Download or read book Ionic Channels of Excitable Membranes written by Bertil Hille and published by Sinauer Associates, Incorporated. This book was released on 1992 with total page 638 pages. Available in PDF, EPUB and Kindle. Book excerpt: This new, fully revised and expanded edition of Ionic Channels of Excitable Membranes includes new chapters on fast chemical synapses, modulation through G protein coupled receptors and second messenger systems, molecules cloning, site directed mutagenesis, and cell biology. It begins with the classical biophysical work of Hodgkin and Huxley and then weaves a description of the known ionic channels together with their biological functions. The book continues by developing the physical and molecular principles needed for explaining permeation, gating, pharmacological modification, and molecular diversity, and ends with a discussion of channel evolution. Ionic Channels of Excitable Membranes is written to be accessible and interesting to biological and physical scientists of all kinds.
Author : Sonsoles Martín-Santamaría
Publisher : Royal Society of Chemistry
ISBN 13 : 1782627006
Total Pages : 392 pages
Book Rating : 4.7/5 (826 download)
Download or read book Computational Tools for Chemical Biology written by Sonsoles Martín-Santamaría and published by Royal Society of Chemistry. This book was released on 2017-11-01 with total page 392 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book offers a fresh perspective on how computational tools can aid the chemical biology research community and drive new research.
