Download or read book The hERG Cardiac Potassium Channel written by Derek J. Chadwick and published by John Wiley & Sons. This book was released on 2005-04-01 with total page 312 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book draws together contributions from basic, pharmaceutical and clinical sciences aimed at a better understanding of the structure and function of hERG and the molecular basis for compound binding. It features regulatory authority perspectives on preferred preclinical test systems and includes topics on hERG channel gating, regulation of functional expression, pharmacological properties of hERG/IKr channels, drug-induced long QT syndrome and preclinical evaluation and regulatory recommendations for assessing QT prolongation risks. Better understanding of the role of the hERG channel in drug-induced cardiac arrhythmias should ultimately lead to the development of important, new and safer medicines.
Download or read book Encyclopedia of Heart Diseases written by M. Gabriel Khan and published by Elsevier. This book was released on 2005-12-14 with total page 678 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Encyclopedia of Heart Diseases is an accurate and reliable source of in-depth information on the diseases that kill more than 12 million individuals worldwide each year. In fact, cardiovascular diseases are more prevalent than the combined incidence of all forms of cancer, diabetes, asthma and leukemia. In one volume, this Encylopedia thoroughly covers these ailments and also includes in-depth analysis of less common and rare heart conditions to round out the volume's scope. Researchers, clinicians, and students alike will all find this resource an invaluable tool for quick reference before approaching the primary literature. * Coverage of more than 200 topics, including: applied pharmacology of current and experimental cardiac drugs, gene therapy, MRI, electron-beam CT, PET scan put in perspective, cardiac tests costs and justification, and new frontiers in cardiovascular research* More than 150 helpful figures and illustrations!* Dr. Khan is a well-published and respected expert in heart and heart diseases
Download or read book Examining the Effects of Activator Compounds on HERG Cardiac Potassium Channel Protective Currents Conducted in Response to Premature Stimulations written by Jacob Kemp and published by . This book was released on 2020 with total page 118 pages. Available in PDF, EPUB and Kindle. Book excerpt: The human ether-a-go-go-related gene (hERG) encodes the rapid delayed rectifier cardiac potassium channel. Vital for repolarization of the myocardium and termination of the cardiac action potential, loss of function in hERG K+ channels can result in Long QT Syndrome Type II (LQTS2). Additionally, hERG channels have been shown to mediate robust repolarizing currents in response to premature depolarizations, reflective of channels remaining in the open state into the refractory period. Thought to be protective against afterdepolarizations, loss of function in this regard may leave individuals susceptible to arrhythmia. Recently, several small molecule activators of hERG have been discovered. The effects of these compounds on the protective currents mediated by hERG channels have yet to be studied. The work presented in this thesis examines the effects of both Type I and II hERG channel activators on protective currents mediated by hERG channels, in the context of an inherited mutation.
Download or read book Pediatric Cardiology written by Alexander Sandor Nadas and published by W.B. Saunders Company. This book was released on 1972 with total page 776 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Pharmacology of Potassium Channels written by Nikita Gamper and published by Springer Nature. This book was released on 2021-09-27 with total page 546 pages. Available in PDF, EPUB and Kindle. Book excerpt: The aim of the present book is to comprehensively review current advances in understanding of genetics, structural biology, pharmacology of potassium channels and their roles in disease as well as to identify current gaps in knowledge. The ultimate goal is to provide a scientific foundation for better understanding of modulatory mechanisms and pharmacology of potassium channels and to use this understanding to drive future drug discovery. This book will be a must-have for academic and industrial scientists interested in physiology, pharmacology, pathology and structure-functional relationships of ion channels. The book will also be helpful for lecturers and students in the college and university classrooms, as well as for anyone interested in the state-of-the art in modern cell biology, physiology and pharmacology.
Download or read book Molecular Basis of Cardiovascular Disease written by Kenneth R. Chien and published by . This book was released on 2004 with total page 760 pages. Available in PDF, EPUB and Kindle. Book excerpt: The 2nd Edition of this heralded companion to Braunwald's Heart Disease explores the molecular mechanisms of cardiology and the scientific advances that are changing the practice of cardiology today. International experts discuss the role of genetics in cardiovascular disease the molecular basis of ischemic disease, thrombosis and hypertension genetic mapping approaches to inherited disorders biologically targeted agents for hypertension and heart failure and much more. Abundant figures and tables illustrate key concepts. Addresses most common cardiovascular problems from a molecular standpoint. Explores developing treatments for cardiovascular problems based on genetics. Provides references to Braunwald's Heart Disease, 6th Edition Examines today's cutting edge advances in molecular cardiology and the future of gene therapy, Examines the implications of cellular cholesterol metabolism in health and disease. . Delivers up-to-date information on understanding the origin of inherited disease.
Download or read book Cardiac Potassium Channel Herg is Regulated by Ubiquitin Ligase Nedd4 2 written by Heidi Victoria Shallow and published by . This book was released on 2011 with total page 134 pages. Available in PDF, EPUB and Kindle. Book excerpt: The cardiac rapidly activating delayed rectifier potassium channel (IKr) is encoded by the human ether-a-go-go related gene (hERG), which is important for repolarization of the cardiac action potential. Reduction in hERG expression levels due to genetic mutations or drugs causes Long QT Syndrome (LQTS). Recently, we demonstrated that ubiquitination of hERG channels is involved in low K+ induced hERG endocytic degradation. Since homeostatic degradation is an important pathway in maintaining hERG membrane expression levels, we investigated the molecular mechanisms for hERG degradation by focusing on the role and consequence of overexpressing the ubiquitin (Ub) ligase, Nedd4-2 (Neural Precursor Cell- Expressed Developmentally Downregulated Gene 4- 2) (Yang & Kumar, 2010). Previous work in the lab demonstrated that Ub plays a role in the internalization of cell-surface hERG channels, and I hypothesized that ubiquitination of hERG channels is facilitated through Nedd4-2. To study the effects of Nedd4-2 on hERG channels, I overexpressed Nedd4-2 in human embryonic kidney (HEK) 293 cells that stably express the hERG channels. Electrophysiological recordings, Western blot, co-immunoprecipitation analysis, and confocal microscopy were performed to identify Nedd4-2's role in hERG expression. The data from whole-cell patch clamp recordings demonstrated that, among hEAG, Kv1.5 and hERG, Nedd4-2 specifically eliminates the hERG channel current. Western blot and confocal imaging analyses showed that Nedd4-2 overexpression led to a significant reduction in mature hERG channels in the plasma membrane. Data obtained using co-immunoprecipitation indicated that Nedd4-2 significantly increases ubiquitinated hERG channels. These data indicate that Nedd4-2 may play a role in hERG homeostatic degradation.
Download or read book 3D QSAR in Drug Design written by Hugo Kubinyi and published by Springer Science & Business Media. This book was released on 2006-04-11 with total page 413 pages. Available in PDF, EPUB and Kindle. Book excerpt: Significant progress has been made in the study of three-dimensional quantitative structure-activity relationships (3D QSAR) since the first publication by Richard Cramer in 1988 and the first volume in the series. 3D QSAR in Drug Design. Theory, Methods and Applications, published in 1993. The aim of that early book was to contribute to the understanding and the further application of CoMFA and related approaches and to facilitate the appropriate use of these methods. Since then, hundreds of papers have appeared using the quickly developing techniques of both 3D QSAR and computational sciences to study a broad variety of biological problems. Again the editor(s) felt that the time had come to solicit reviews on published and new viewpoints to document the state of the art of 3D QSAR in its broadest definition and to provide visions of where new techniques will emerge or new appli- tions may be found. The intention is not only to highlight new ideas but also to show the shortcomings, inaccuracies, and abuses of the methods. We hope this book will enable others to separate trivial from visionary approaches and me-too methodology from in- vative techniques. These concerns guided our choice of contributors. To our delight, our call for papers elicited a great many manuscripts.
Download or read book Cardiac Potassium Channel Disorders An Issue of Cardiac Electrophysiology Clinics written by Mohammad Shenasa and published by Elsevier Health Sciences. This book was released on 2016-06-10 with total page 265 pages. Available in PDF, EPUB and Kindle. Book excerpt: This issue of Cardiac Electrophysiology Clinics, edited by Drs. Mohammad Shenasa and Stanley Nattel, will review Cardiac Potassium Channel Disorders in depth. Topics covered include but are not limited to: Molecular Biology of Cardiac Potassium Channels; Genetic Control of Potassium Channels; Potassium Channel Remodeling in Heart Disease; Gender-specific Effects of Potassium Channel Blockers; Pharmacogenetics of Potassium Channel Blockers; Multichannel Blockers; Selective Potassium Channel Blockers; and Proarrhythmic and Torsadogenic Effects of Potassium Channel Blockers in Patients.
Download or read book Computational Toxicology written by Sean Ekins and published by John Wiley & Sons. This book was released on 2018-02-13 with total page 450 pages. Available in PDF, EPUB and Kindle. Book excerpt: A key resource for toxicologists across a broad spectrum of fields, this book offers a comprehensive analysis of molecular modelling approaches and strategies applied to risk assessment for pharmaceutical and environmental chemicals. Provides a perspective of what is currently achievable with computational toxicology and a view to future developments Helps readers overcome questions of data sources, curation, treatment, and how to model / interpret critical endpoints that support 21st century hazard assessment Assembles cutting-edge concepts and leading authors into a unique and powerful single-source reference Includes in-depth looks at QSAR models, physicochemical drug properties, structure-based drug targeting, chemical mixture assessments, and environmental modeling Features coverage about consumer product safety assessment and chemical defense along with chapters on open source toxicology and big data
Download or read book Electrical Diseases of the Heart written by Ihor Gussak and published by Springer Science & Business Media. This book was released on 2008-09-08 with total page 600 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a unique contemporary and succinct distillation of the current status of recently delineated electrical diseases of the heart, emphasizing their common and diverse clinical features. The latest developments in the field of experimental and clinical cardiac electrophysiology, genetics, pharmacology and interventional therapies of various clinical arrhythmogenic entities are featured and discussed in terms of recent advances in basic and clinical science. The book is divided into seven major parts. Each part consists of chapters (total of 64) dealing with related topics.
Download or read book Regulation of Cardiac Potassium Channels in Health and Disease written by Hannah Aizad Ledford and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Background: Cardiac potassium channels are implicated in a range of inherited and acquired ion channelopathies. Consequently, the regulation of potassium channels is a critical process; malfunction of which results in changes to membrane surface expression, current density, and channel kinetics. Decreases or increases in current can arise from defects in the channels themselves or from dysregulation by chaperone, trafficking, degradation, or accessory proteins, in addition to intracellular and extracellular factors (e.g. Ca2+ concentrations, second messenger signaling molecules, hormonal influences, ion concentrations, and pH). Here, we investigated the effects of regulatory mechanisms on potassium channel function and cardiac arrhythmogenesis. We evaluated the roles of interacting proteins on atrial and ventricular K+ channel function. Using heterologous expression systems (HEK 293 cells), mouse models, and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), we evaluated the impacts of quality control mechanisms on the human ether-à-go-go related gene (hERG) K+ channel; interacting proteins on small-conductance Ca2+-activated K+ channels (SK); and anion exchanger Slc26a6 on cardiac excitability and action potential. Specifically, we tested the hypotheses that E3 ubiquitin ligase, RNF207, regulates hERG channel expression and function through endoplasmic reticulum (ER)-associated degradation (chapter 2); calmodulin (CaM) mutants decrease SK2 current density through regulation of channel activation kinetics (chapter 3); [alpha]-actinin and filamin A regulate SK2 channel trafficking and surface expression (chapter 4); and Slc26a6 regulates cardiac excitability and action potential via its effects on intracellular pH and membrane potential (chapter 5). Methods and Results: To further evaluate these effects, we utilized a combination of electrophysiology, molecular biology, and imaging techniques. Whole-cell voltage-clamp, perforated patch action potential recordings, co-immunoprecipitation, degradation and ubiquitinylation assays, and immunofluorescence through confocal microscopy and stimulated emission depletion (STED) high-resolution microscopy were used in this study. We found that wild-type RNF207 is able to ubiquitinylate mutant hERG subunits (T613M; hERG[subscript T613M]), whereas mutant RNF207 (G603fs; RNF207[subscript G603fs]) fails to tag mutant hERG for degradation, allowing significant reduction in current density. SK2 channel surface expression was shown to be significantly enhanced by alpha-actinin and filamin a coexpression. SK2 current density was regulated by Ca2+-CaM activation, which was altered in the presence of CaM mutants. Lastly, we found that knockdown of Slc26a6 resulted in significantly prolonged action potential duration, decreased calcium transients, and intracellular pH irregularities. Conclusions Regulatory mechanisms play a key role in K+ channel expression and function. Potentially detrimental effects of heterozygously inherited channel mutations, which would otherwise be masked, may be revealed in the case of simultaneously inherited mutations in quality control mechanisms. Consequently, the effects of mutations in interacting proteins, cardiac ion channels or exchangers, and intracellular messengers may be widespread and warrants further study.
Download or read book Anesthetic Pharmacology written by Alex S. Evers and published by Cambridge University Press. This book was released on 2011-03-10 with total page 2902 pages. Available in PDF, EPUB and Kindle. Book excerpt: In recent years our understanding of molecular mechanisms of drug action and interindividual variability in drug response has grown enormously. Meanwhile, the practice of anesthesiology has expanded to the preoperative environment and numerous locations outside the OR. Anesthetic Pharmacology: Basic Principles and Clinical Practice, 2nd edition, is an outstanding therapeutic resource in anesthesia and critical care: Section 1 introduces the principles of drug action, Section 2 presents the molecular, cellular and integrated physiology of the target organ/functional system and Section 3 reviews the pharmacology and toxicology of anesthetic drugs. The new Section 4, Therapeutics of Clinical Practice, provides integrated and comparative pharmacology and the practical application of drugs in daily clinical practice. Edited by three highly acclaimed academic anesthetic pharmacologists, with contributions from an international team of experts, and illustrated in full colour, this is a sophisticated, user-friendly resource for all practitioners providing care in the perioperative period.
Download or read book CARDIAC POTASSIUM CHANNEL HERG IS REGULATED BY UBIQUITIN LIGASE NEDD4 2 written by HEIDI. SHALLOW and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Channelopathies in Heart Disease written by Dierk Thomas and published by Springer. This book was released on 2018-12-26 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides an expert overview on ion channel-related arrhythmia mechanisms, and describes important advances in our understanding of how ion channel dysfunction causes cardiac disease. Both, scientific findings and clinical implications are presented and discussed by scientists who have considerably contributed to the field. The book is organized in three parts: part I treats the molecular and electrophysiological mechanisms of function and dysfunction of ion channels, part II focuses on genetics and clinical findings, whereas part III describes novel research techniques, the use of stem cells and animal models and provides an outlook on future investigations and applications. The book is written for scientists in Cardiovascular Biology and Neuroscience and will be of general interest to Medical Doctors in Cardiology, Cardiac Electrophysiology and related disciplines.
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 Antitargets written by Roy J. Vaz and published by John Wiley & Sons. This book was released on 2008-04-09 with total page 504 pages. Available in PDF, EPUB and Kindle. Book excerpt: This practice-oriented handbook surveys current knowledge on the prediction and prevention of adverse drug reactions related to off-target activity of small molecule drugs. It is unique in collating the current approaches into a single source, and includes several highly instructive case studies that may be used as guidelines on how to improve drug development projects. With its large section on ADME-related effects, this is key knowledge for every drug developer.
