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 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 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 Ubiquitination and Transmembrane Signaling written by and published by Academic Press. This book was released on 2016-06-29 with total page 431 pages. Available in PDF, EPUB and Kindle. Book excerpt: Progress in Molecular Biology and Translational Science provides a forum for discussion of new discoveries, approaches, and ideas in molecular biology. It contains contributions from leaders in their fields and abundant references. Contains contributions from leading authorities Informs and updates on all the latest developments in the field

Download or read book Ion Channel Trafficking and Cardiac Arrhythmias written by Marcel A.G. van der Heyden and published by Frontiers Media SA. This book was released on 2018-12-06 with total page 123 pages. Available in PDF, EPUB and Kindle. Book excerpt: A well-adjusted expression of cardiac ion channels at the sarcolemma is of crucial importance for normal action potential formation and thus cardiac function. The cellular processes that transport channel proteins from the endoplasmic reticulum towards specified regions on the sarcolemmal membrane, and subsequently take them from the plasma membrane to the protein degradation machinery are commonly known as trafficking. The research field recognizes that aberrant channel trafficking stands at the basis of many congenital and acquired arrhythmias. The collection of papers in this eBook provides state-of-the-art insight into the world of ion channel trafficking research.

Download or read book Enzymes Advances in Research and Application 2013 Edition written by and published by ScholarlyEditions. This book was released on 2013-06-21 with total page 696 pages. Available in PDF, EPUB and Kindle. Book excerpt: Enzymes—Advances in Research and Application: 2013 Edition is a ScholarlyEditions™ book that delivers timely, authoritative, and comprehensive information about Transferases. The editors have built Enzymes—Advances in Research and Application: 2013 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Transferases in this book to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Enzymes—Advances in Research and Application: 2013 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.

Download or read book Cardiovascular Signaling in Health and Disease written by Narasimham L. Parinandi and published by Springer Nature. This book was released on 2022-09-21 with total page 535 pages. Available in PDF, EPUB and Kindle. Book excerpt: This contributed volume focuses on cardiovascular diseases (CVDs), and explores the ways in which signaling mechanisms at the biochemical, molecular, and cellular levels in the blood vessels (vascular) and heart contribute to the underlying causes of development and progression of the CVDs. This volume covers unique topics such as oxidant signaling in vascular and heart diseases and health, cytoskeletal signaling in vascular health and disease, phospholipase signaling in CVDs, lipid signaling in vascular and myocardial health and diseases, and drug discovery in cellular signaling for cardiovascular diseases. This book assembles the most important discoveries made by leaders on the cellular signaling mechanisms operating behind the development and progression of life-threatening CVDs. It is an extremely useful resource for the investigators in the field of CVDs, and opens the discussion for further discovery of efficient management and effective treatment of the CVDs.

Download or read book Seldin and Giebisch s The Kidney written by Robert J. Alpern and published by Elsevier. This book was released on 2007-10-10 with total page 2922 pages. Available in PDF, EPUB and Kindle. Book excerpt: A classic nephrology reference for over 20 years, Seldin & Giebisch’s The Kidney, is the acknowledged authority on renal physiology and pathophysiology. The fourth edition follows the changed focus of nephrology research to the study of how individual molecules work together to affect cellular and organ function, emphasizing the mechanisms of disease. With over 40 new chapters and over 1000 illustrations, this edition offers the most in-depth discussion anywhere of the physiologic and pathophysiologic processes of renal disease. Comprehensive, authoritative coverage progresses from molecular biology and cell physiology to clinical issues regarding renal function and dysfunction. If you research the development of normal renal function or the mechanisms underlying renal disease, Seldin & Giebisch’s The Kidney is your number one source for information. * Offers the most comprehensive coverage of fluid and electrolyte regulation and dysregulation in 51 completely revised chapters unlike Brenner & Rector's The Kidney which devotes only 7 chapters to this topic.* Includes 3 sections, 31 chapters, devoted to regulation and disorders of acid-base homeostasis, and epithelial and nonepithelial transport regulation. Brenner & Rector's only devotes 5 chapters to these topics.* Previous three editions edited by Donald Seldin and Gerhard Giebisch, world renowned names in nephrology. The title for the fourth edition has been changed to reflect their considerable work on previous editions and they have also written the forward for this edition. * Over 20 million adults over age 20 have chronic kidney disease with the number of people diagnosed doubling each decade making it America's ninth leading cause of death.

Download or read book Cardiac Cytoarchitecture written by Elisabeth Ehler and published by Springer. This book was released on 2015-03-03 with total page 320 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents a collection of expert reviews on different subcellular compartments of the cardiomyocyte, addressing fundamental questions such as how these compartments are assembled during development, how they are changed in and by disease and which signaling pathways have been implicated in these processes so far. As such, it offers the first overview of the cell biology of heart disease of its kind, addressing the needs of cell biology students specializing in vascular and cardiac biology, as well as those of cardiologists and researchers in the field of cell biology.

Download or read book Cardiac Electrophysiology From Cell to Bedside E Book written by Douglas P. Zipes and published by Elsevier Health Sciences. This book was released on 2009-05-06 with total page 1183 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cardiac Electrophysiology: From Cell to Bedside defines the entire state of current scientific and clinical knowledge in this subspecialty. In response to the many major recent developments in the field, Drs. Zipes and Jalife have completely updated this modern classic, making the 5th Edition the most significant revision yet. From our latest understanding of ion channels, molecular genetics, and cardiac electrical activity through newly recognized syndromes, unique needs of special patient populations, and new diagnostic and therapeutic options, you'll find all the state-of-the-art guidance you need to make informed, effective clinical decisions. What's more, a significantly restructured organization, a new full-color layout, and full-text online access make reference easier than ever. Integrates the latest scientific understanding of arrhythmias with the newest clinical applications, giving you an informed basis for choosing the right treatment and management options for each patient. Synthesizes the knowledge of preeminent authorities in cardiology, physiology, pharmacology, pediatrics, biophysics, pathology, cardiothoracic surgery, and biomedical engineering from around the world, giving you a well-rounded, expert grasp of every issue that affects your patient management. Contains 24 new chapters (listed below) as well as exhaustive updates throughout, to keep you current with new scientific knowledge, newly discovered arrhythmia syndromes, and new diagnostic and therapeutic techniques. Developmental Regulation of Cardiac Ion Channels Neural Mechanisms of Initiating and Maintaining Arrhythmias Single Nucleotide Polymorphisms and Acquired Cardiac Arrhythmias Inheritable Sodium Channel Diseases Inheritable Potassium Channel Diseases Inheritable Diseases of Intracellular Calcium Regulation Morphological Correlates of Atrial Arrhythmias Andersen-Tawil Syndrome Timothy Syndrome Progressive Cardiac Conduction Disease Sudden Infant Death Syndrome Arrhythmias in Patients with Neurologic Disorders Autonomic Testing Cardiac Resynchronization Therapy Energy Sources for Catheter Ablation Linear Lesions to Ablate Atrial Fibrillation Catheter Ablation of Ventricular Arrhythmias in Patients with Structural Heart Disease Catheter Ablation of Ventricular Arrhythmias in Patients without Structural Heart Disease Catheter Ablation in Patients with Congenital Heart Disease Features a completely new section on "Arrhythmias in Special Populations" that explores arrhythmias in athletes ... gender differences in arrhythmias ... arrhythmias in pediatric patients ... and sleep-disordered breathing and arrhythmias. Offers an attractive new full-color design featuring color photos, tables, flow charts, ECGs, and more, making clinically actionable information easy to find and absorb at a glance. Includes full-text online access via Expert Consult, making reference easier for busy practitioners.

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

Download or read book Index Medicus written by and published by . This book was released on 2004 with total page 2160 pages. Available in PDF, EPUB and Kindle. Book excerpt: Vols. for 1963- include as pt. 2 of the Jan. issue: Medical subject headings.

Download or read book Zipes and Jalife s Cardiac Electrophysiology From Cell to Bedside written by Jose Jalife and published by Elsevier Health Sciences. This book was released on 2021-12-16 with total page 1709 pages. Available in PDF, EPUB and Kindle. Book excerpt: Fully updated from cover to cover, Zipes and Jalife’s Cardiac Electrophysiology: From Cell to Bedside, 8th Edition, provides the comprehensive, multidisciplinary coverage you need—from new knowledge in basic science to the latest clinical advances in the field. Drs. José Jalife and William Gregory Stevenson lead a team of global experts who provide cutting-edge content and step-by-step instructions for all aspects of cardiac electrophysiology. Packs each chapter with the latest information necessary for optimal basic research as well as patient care. Covers new technologies such as CRISPR, protein research, improved cardiac imaging, optical mapping, and wearable devices. Contains significant updates in the areas of molecular biology and genetics, iPSCs (induced pluripotent stem cells), embryonic stem cells, precision medicine, antiarrhythmic drug therapy, cardiac mapping with advanced techniques, and ablation technologies including stereotactic radioablation. Includes 47 new standalone chapters that are organized into discrete topics for improved access. Discusses extensive recent progress in the understanding, diagnosis, and management of arrhythmias, including new clinical insights on atrial fibrillation and stroke prevention, new advances in the understanding of ventricular arrythmias in genetic disease, and advances in implantable devises and infection management. Features 1,600 high-quality photographs, anatomic and radiographic images, electrocardiograms, tables, algorithms, and more., with additional figures, tables, and videos online. Recipient of a 2018 Highly Commended award from the British Medical Association.

Download or read book Cardiac Electrophysiology from Cell to Bedside written by Douglas P. Zipes and published by Elsevier Health Sciences. This book was released on 2013-10-25 with total page 1395 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cardiac Electrophysiology: From Cell to Bedside puts the latest knowledge in this subspecialty at your fingertips, giving you a well-rounded, expert grasp of every cardiac electrophysiology issue that affects your patient management. Drs. Zipes, Jalife, and a host of other world leaders in cardiac electrophysiology use a comprehensive, multidisciplinary approach to guide you through all of the most recent cardiac drugs, techniques, and technologies. Get well-rounded, expert views of every cardiac electrophysiology issue that affects your patient management from preeminent authorities in cardiology, physiology, pharmacology, pediatrics, biophysics, pathology, cardiothoracic surgery, and biomedical engineering from around the world. Visually grasp and easily absorb complex concepts through an attractive full-color design featuring color photos, tables, flow charts, ECGs, and more! Integrate the latest scientific understanding of arrhythmias with the newest clinical applications, to select the right treatment and management options for each patient. Stay current on the latest advancements and developments with sweeping updates and 52 NEW chapters - written by many new authors - on some of the hottest cardiology topics, such as new technologies for the study of the molecular structure of ion channels, molecular genetics, and the development of new imaging, mapping and ablation techniques. Get expert advice from Dr. Douglas P. Zipes - a leading authority in electrophysiology and editor of Braunwald's Heart Disease and the Heart Rhythm Journal - and Dr. Jose Jalife - a world-renowned leader and researcher in basic and translational cardiac electrophysiology. Access the full text online at Expert Consult, including supplemental text, figures, tables, and video clips. Your purchase entitles you to access the web site until the next edition is published, or until the current edition is no longer offered for sale by Elsevier, whichever occurs first. If the next edition is published less than one year after your purchase, you will be entitled to online access for one year from your date of purchase. Elsevier reserves the right to offer a suitable replacement product (such as a downloadable or CD-ROM-based electronic version) should online access to the web site be discontinued.

Download or read book Cardiac Repolarization written by Ihor Gussak and published by Springer Science & Business Media. This book was released on 2003-03-13 with total page 549 pages. Available in PDF, EPUB and Kindle. Book excerpt: A comprehensive review of all the latest developments in cardiac electrophysiology, focusing on both the clinical and experimental aspects of ventricular repolarization, including newly discovered clinical repolarization syndromes, electrocardiographic phenomena, and their correlation with the most recent advances in basic science. The authors illuminate the basic electrophysiologic, molecular, and pharmacologic mechanisms underlying ventricular repolarization, relate them to specific disease conditions, and examine the future of antiarrhythmic drug development based on both molecular and electrophysiological properties. They also fully review the clinical presentation and management of specific cardiac repolarization conditions.

Download or read book Protein Blood Group Antigens of the Human Red Cell written by Peter Agre and published by . This book was released on 1992 with total page 296 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Platform Technologies in Drug Discovery and Validation written by and published by Academic Press. This book was released on 2017-11-21 with total page 692 pages. Available in PDF, EPUB and Kindle. Book excerpt: Platform Technologies in Drug Discovery and Validation, Volume 50, the latest release in the Annual Reports in Medicinal Chemistry series, provides timely and critical reviews of important topics in medicinal chemistry, with an emphasis on emerging topics in the biological sciences. Topics covered in this new volume include DELT, Oligos: ASO, siRNA, CRISPR, Micro-fluidic chemistry, High throughput screening, Kinase-centric computational drug development, Virtual Screening, Phenotypic screening, PROTACS, Chemical Biology, Fragment-based lead generation, Antibody-Drug Conjugates, Antibody-recruiting small molecules, Deuteration, and Peptides. Unique for its treatment of platform technologies for medicinal chemistry and target validation Provides a single, rich volume that summaries a broad spectrum of expertise relevant to the field Presents state-of-the-art summaries of platform technologies