Download or read book Endogenous and Exogenous Molecules Modulating Voltage Gated Potassium Channels written by Damon Frampton and published by Linköping University Electronic Press. This book was released on 2024-10-02 with total page 145 pages. Available in PDF, EPUB and Kindle. Book excerpt: The superfamily of voltage-gated potassium (KV) channels is crucial for the normal function of several tissues and represents an attractive pharmacological target for treating disorders such as epilepsy and cardiac arrhythmias. However, any drug designed to target a KV channel must be capable of discriminating between different members within the superfamily, lest they plague the user with deleterious side effects. Such rational design requires structural and functional insight into how the selectivity of a molecule can be tailored to suit the intended target. This thesis combines the use of electrophysiological and computational techniques to investigate the molecular basis for how the function of hKV7 and hERG channels can be modulated by different lipophilic compounds with known or suspected effects on ion channels. These include polyunsaturated fatty acids (PUFAs), cannabidiol (CBD), and synthetic cannabinoid receptor agonists (SCRAs). Using the two-electrode voltage clamp technique on Xenopus oocytes, we find that both PUFAs and CBD modulate the function of hKV7 channels in subtype-specific manners. PUFAs facilitated the activation of hKV7 channels, except for hKV7.4 channels which were instead inhibited. Molecular dynamics simulations revealed that structural differences in the voltage-sensing domain of hKV7.4 conferred a unique, inhibitory PUFA interaction site absent in the other hKV7 subtypes. Once this site was neutralised by mutagenesis, PUFAs facilitated hKV7.4 activation. In the case of CBD, we observed three different responses: inhibition of channels with hKV7.1 subunits, potentiated voltage-sensitivity of channels with hKV7.2 or hKV7.3 subunits and enhanced maximum conductance of channels with hKV7.4 or hKV7.5 subunits. However, these responses were evoked from the same interaction site in the pore domain, indicating a more complex subtype-specific mechanism of action. Finally, using an automated patch-clamp system we screened 36 different SCRAs on the cardiac channels responsible for repolarisation: hERG and hKV7.1/KCNE1. We find 28 of the SCRAs to be inhibitors of hERG and 22 to be inhibitors of hKV7.1/KCNE1. Molecular dynamics simulations suggest the increased susceptibility of hERG to SCRA-mediated inhibition may be due to a unique central cavity site that is absent from the pore domain of hKV7.1/KCNE1. In conclusion, structurally diverse lipophilic molecules of endogenous and exogenous origins can interact with KV channels and influence their function by enhancing or interfering with functional domains. In some instances, structural differences in the channel protein can explain the discrepancies in pharmacology. These findings have implications for both pharmacology (informing rational drug design) and toxicology (identifying targets through which adverse effects may occur).
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.
Download or read book Low voltage activated T type Calcium Channels written by Richard W. Tsien and published by . This book was released on 1998 with total page 420 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Systems Biology of Free Radicals and Antioxidants written by Ismail Laher and published by Springer. This book was released on 2014-06-16 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The focus of this collection of illustrated reviews is to discuss the systems biology of free radicals and anti-oxidants. Free radical induced cellular damage in a variety of tissues and organs is reviewed, with detailed discussion of molecular and cellular mechanisms. The collection is aimed at those new to the field, as well as clinicians and scientists with long standing interests in free radical biology. A feature of this collection is that the material also brings insights into various diseases where free radicals are thought to play a role. There is extensive discussion of the success and limitations of the use of antioxidants in several clinical settings.
Download or read book Ion Channel Pharmacology written by Bernat Soria and published by . This book was released on 1998 with total page 498 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Modulation of Ion Channels and Ionic Pumps by Fatty Acids Implications in Physiology and Pathology written by Mario Diaz and published by Frontiers Media SA. This book was released on 2019-02-05 with total page 135 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Neurotransmitter Release written by Hugo J. Bellen and published by Oxford University Press, USA. This book was released on 1999 with total page 466 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides the reader with background information on neurotransmitter release. Emphasis is placed on the rationale by which proteins are assigned specific functions rather than just providing facts about function.
Download or read book Cannabis Use Neurobiology Psychology and Treatment written by Colin R Martin and published by Elsevier. This book was released on 2023-06-02 with total page 672 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cannabis Use, Neurobiology, Psychology, and Treatment offers readers a comprehensive reference on neurological changes, both transient and long-term, and other factors surrounding the use of these compounds and extracts. With coverage of both natural and synthetic cannabinoids, this broad coverage allows readers to learn about both adverse and non-adverse effects, including reactivity to pain, changes in behavior, and neuroactivity. This volume provides a platform for research on the effects of these compounds in brain function and neurological dysfunction. Extracts from the Cannabis sativa plant contain scores of psychoactive compounds in addition to the principal agent tetrahydrocannabinol, many of which are neuroactive. Summarizes cannabis and cannabinoid research in relation to neurological function Contains chapter abstracts, key facts, a dictionary and a summary Covers the neuroactivity of multiple Cannabis compounds beyond tetrahydrocannabinol Includes conditions like depression, anxiety, Parkinson’s, psychosis, and epilepsy Discusses brain structure and brain development, including functional connectivity
Download or read book New Non opioid Analgesics Understanding Molecular Mechanisms on the Basis of Patch clamp and chemical Studies written by Boris V. Krylov and published by Bentham Science Publishers. This book was released on 2017-06-12 with total page 211 pages. Available in PDF, EPUB and Kindle. Book excerpt: The monograph is a summary of methods used to study pain receptors and the results obtained in some experiments designed to study the effect of non-opioid analgesics. The molecular mechanisms of nociceptive information control in primary sensory nociceptive neurons are described based on investigations of the membrane signaling cascade (opioid-like receptor → Na+,K+-ATPase → NaV1.8 channel) observed by the authors. Based on this data, the authors conclude that the modulation of NaV1.8 channels responsible for the coding of noxious signals can be carried out due to two novel targeting mechanisms. The first of these is the activation of opioid-like receptors; the second is the activation of Na+/K+-ATPase as a signal transducer. The development of a novel class of analgesics that trigger these mechanisms should lead to a successful solution to the problem of chronic pain relief. Chapters of the monograph cover the general methods used in studying nociceptive pain (including the patch-clamp method), and the mechanism behind the binding of different ligands to these receptors such gamma-pyrones, gamma-pyridines and cardiotonic steroids. This monograph is a valuable reference for neuroscientists, pharmacologists and allied researchers studying pain receptors for the development of safe and effective analgesics.
Download or read book Kv7 Channels Structure Physiology and Pharmacology written by Thomas Andrew Jepps and published by Frontiers Media SA. This book was released on 2021-07-02 with total page 239 pages. Available in PDF, EPUB and Kindle. Book excerpt: This Research Topic was in partnership with CAP Partner for the International Kv7 Channels Symposium held in Naples, Italy on September 2019.
Download or read book Ion Channel Regulation written by and published by Academic Press. This book was released on 1999-04-13 with total page 339 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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
Download or read book Sigma Receptors written by Rae R. Matsumoto and published by Springer Science & Business Media. This book was released on 2007-02-15 with total page 416 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides an update on sigma receptors, and summarizes recent advances in the medicinal chemistry, molecular biology, and cell biology of sigma receptors. It describes the functional effects mediated by these receptors and the potential clinical implications of these actions. The information is put in a historical perspective. This provides a launching point from which future studies and research directions can easily be developed.
Download or read book The Endothelium written by Michel Félétou and published by Morgan & Claypool Publishers. This book was released on 2011 with total page 309 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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
Download or read book The Arterial Chemoreceptors written by Yoshiaki Hayashida and published by Springer Science & Business Media. This book was released on 2006-04-24 with total page 360 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book represents an updated review of the physiology of the carotid body chemoreceptors. It contains results in the topics at the frontiers of future developments in O2-sensing in chemoreceptor cells. Additionally, this volume provides data from studies carried out in other O2-sensing tissues including pulmonary vasculature and erythropoietin producing cells. It is a prime source of information and a guideline for arterial chemoreception researchers.
Download or read book Potassium Channels in Cardiovascular Biology written by Stephen L. Archer and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 962 pages. Available in PDF, EPUB and Kindle. Book excerpt: Potassium channels (K+) are membrane-spanning proteins which serve many important functions and are becoming a hot topic in physiology. K+ channels determine or modulate many functions of vascular smooth muscle, endothelial and inflammatory cells, and thus are central to regulation of arterial tone and control of cell proliferation. They are also promising targets for antihypertensive treatments with drugs which open and close specific types of K+ channels, making for an active field of research. With their ability to control vascular tone, voltage-gated K+ channels play a significant role in both pulmonary and systemic hypertension as well as in cardiac arrhythmias. This book will highlight the latest discoveries by leading researchers pertaining to the role of K+ channels in the heart and blood vessels in normal physiology and a variety of disease states.
Download or read book Neuromuscular Disorders Management and Treatment E Book written by Tulio E. Bertorini and published by Elsevier Health Sciences. This book was released on 2010-09-08 with total page 469 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neuromuscular Disorders presents a multi-disciplinary approach to the management and therapeutic treatment of the full range of neuromuscular disorders and resulting complications. Dr. Tulio Bertorini and a contributing team of the world’s leading authorities in the field provide the latest tools and strategies for minimizing disability and maximizing quality of life. Effectively treat your patients using the latest management tools and targeted therapeutic strategies. Manage all neuromuscular disorders as well as resulting complications through comprehensive coverage of diagnosis and evaluations, treatments, and outcomes. Apply the multi-disciplinary approach of an expert in clinical neuromuscular care and a team of world-renown contributors. Easily refer to tools for diagnosis, treatment algorithms, and drug tables included throughout the text.
Download or read book Comprehensive Toxicology written by and published by Elsevier. This book was released on 2017-12-01 with total page 8639 pages. Available in PDF, EPUB and Kindle. Book excerpt: Comprehensive Toxicology, Third Edition, Fifteen Volume Set discusses chemical effects on biological systems, with a focus on understanding the mechanisms by which chemicals induce adverse health effects. Organized by organ system, this comprehensive reference work addresses the toxicological effects of chemicals on the immune system, the hematopoietic system, cardiovascular system, respiratory system, hepatic toxicology, renal toxicology, gastrointestinal toxicology, reproductive and endocrine toxicology, neuro and behavioral toxicology, developmental toxicology and carcinogenesis, also including critical sections that cover the general principles of toxicology, cellular and molecular toxicology, biotransformation and toxicology testing and evaluation. Each section is examined in state-of-the-art chapters written by domain experts, providing key information to support the investigations of researchers across the medical, veterinary, food, environment and chemical research industries, and national and international regulatory agencies. Thoroughly revised and expanded to 15 volumes that include the latest advances in research, and uniquely organized by organ system for ease of reference and diagnosis, this new edition is an essential reference for researchers of toxicology. Organized to cover both the fundamental principles of toxicology and unique aspects of major organ systems Thoroughly revised to include the latest advances in the toxicological effects of chemicals on the immune system Features additional coverage throughout and a new volume on toxicology of the hematopoietic system Presents in-depth, comprehensive coverage from an international author base of domain experts
