Author: Junyang Lou
Publisher:
ISBN:
Category :
Languages : en
Pages : 240

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Author: Gregory R. Bock
Publisher: John Wiley & Sons
ISBN: 9780471485308
Category : Science
Languages : en
Pages : 258

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Book Description
Recent progress has led to a better understanding of the molecular structure of sodium channels, how they work and the mechanisms that restrict their expression to particular cell types. This book explains how these channels are modulated in various pathological states to enable the development of therapeutic strategies based on sodium channel restoration. The authors present the most current research on sodium channels and neuronal function. Brings together both the basic biology and biophysics with detailed consideration of the medical applications in chronic pain and epilepsy. Includes coverage of channelopathies, sodium channel gene expression, the modulation of sodium channels, and molecular mechanisms of gating and drug block of sodium channels.

Author: Agnes Sara Zybura
Publisher:
ISBN:
Category :
Languages : en
Pages : 622

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Book Description
Voltage-gated sodium channels (Navs) undergo remarkably complex modes of modulation to fine tune membrane excitability and neuronal firing properties. In neurons, the isoform Nav1.6 is highly enriched at the axon initial segment and nodes, making it critical for the initiation and propagation of neuronal impulses. Thus, Nav1.6 modulation and dysfunction may profoundly impact the input-output properties of neurons in normal and pathological conditions. Phosphorylation is a powerful and reversible mechanism that exquisitely modulates ion channels. To this end, the multifunctional calcium/calmodulin-dependent protein kinase II (CaMKII) can transduce neuronal activity through phosphorylation of diverse substrates to serve as a master regulator of neuronal function. Because Nav1.6 and CaMKII are independently linked to excitability disorders, I sought to investigate modulation of Nav1.6 function by CaMKII signaling to reveal an important mechanism underlying neuronal excitability. Multiple biochemical approaches show Nav1.6 is a novel substrate for CaMKII and reveal multi-site phosphorylation within the L1 domain; a hotspot for post-translational regulation in other Nav isoforms. Consistent with these findings, pharmacological inhibition of CaMKII reduces transient and persistent sodium currents in Purkinje neurons. Because Nav1.6 is the predominant sodium current observed in Purkinje neurons, these data suggest that Nav1.6 may be modulated through CaMKII signaling. In support of this, my studies demonstrate that CaMKII inhibition significantly attenuates Nav1.6 transient and persistent sodium currents and shifts the voltage-dependence of activation to more depolarizing potentials in heterologous cells. Interestingly, I show that these functional effects are likely mediated by CaMKII phosphorylation of Nav1.6 at S561 and T642, and that each phosphorylation site regulates distinct biophysical characteristics of the channel. These findings are further extended to investigate CaMKII modulation of disease-linked mutant Nav1.6 channels. I show that different Nav1.6 mutants display distinct responses to CaMKII modulation and reveal that acute CaMKII inhibition attenuates gain-of-function effects produced by mutant channels. Importantly, computational simulations modeling the effects of CaMKII inhibition on WT and mutant Nav1.6 channels demonstrate dramatic reductions in neuronal excitability in Purkinje and cortical pyramidal cell models. Together, these findings suggest that CaMKII modulation of Nav1.6 may be a powerful mechanism to regulate physiological and pathological neuronal excitability.

Author: Peter C. Ruben
Publisher: Springer Science & Business Media
ISBN: 3642415881
Category : Medical
Languages : en
Pages : 328

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Book Description
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: Angus C. Nairn
Publisher: MDPI
ISBN: 3039281062
Category : Science
Languages : en
Pages : 318

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Book Description
The Neuroproteomics Special Issue overviews the unique challenges that must be addressed to carry out meaningful MS/proteomics analyses on neural tissues and the technologies that are available to meet these challenges. The articles on Alzheimer’s disease, addiction, and schizophrenia illustrate how MS/proteomics technologies can be used to improve our ability to diagnose and understand the molecular basis for neurological diseases. Several articles will be of interest to investigators beyond the field of neurological disorders. The review on the discovery of biofluid biomarkers of neurodegenerative dementias will be of interest to investigators searching for other disease biomarkers. Similarly, the review on the role of neuroproteomics in elucidating mechanisms of drug addiction provides an overview of the utility of MS/proteomics approaches for addressing critical questions in addiction neuroscience that should be applicable to investigators involved in virtually any area of biomedical research. Likewise, the article on developing targeted MS approaches for quantifying postsynaptic density proteins will be useful for any investigator who wishes to design targeted assays for virtually any protein. Finally, the peroxidase-mediated proximity labeling technology, described in the article on mapping the proteome of the synaptic cleft, will be of interest to investigators interested in mapping other spatially restricted proteomes.

Author: Mohamed Chahine
Publisher: Frontiers E-books
ISBN: 2889191281
Category :
Languages : en
Pages : 119

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Book Description
It is our pleasure to co-edit a Research Topic on voltage-gated sodium channels pharmacology and related diseases. We are in a process to inviting submissions of novel research article, state-of-the-art review papers and viewpoints on this topic. All the papers will follow a peer-review process according to the guidelines of Frontiers in Pharmacology. Voltage-gated sodium channel play a critical role in electrical signalling in many excitable cells such as neurons, skeletal muscle cells and cardiac myocytes. They are responsible for the initiation and the propagation of action potential, allowing integration of higher processes. They are formed by one alpha subunit that forms the pore of the channel and one or several regulatory subunits. Sodium channels are the target for local anaesthetics, antiarrhythmic drugs, and anticonvulsants. This class of ion channels is prime target to several toxins. Recently, a number of mutations in sodium channels that often results in alterations of rapid channel gating have been identified and linked to human diseases. Such channelopathies cause periodic paralysis, myotonia, long QT syndrome and other cardiac conductance disturbances, pain, hemiplegic migraine, and epilepsy. Sodium channels play also a negative role in malignant cellular proliferation, chronic pain, and other diseases. Considering these crucial physiological and pathological implications, it is not surprising that sodium channels have been and still are key targets for drug development. This Research Topic of Frontiers of Pharmacology of Ion Channels and Channelopathies will focus on this important class of ion channels how they operate, their pharmacology and their implication in diseases.

Author: Douglas P. Zipes
Publisher: Elsevier Health Sciences
ISBN: 0323448887
Category : Medical
Languages : en
Pages : 1429

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Book Description
Rapid advancements in cardiac electrophysiology require today’s health care scientists and practitioners to stay up to date with new information both at the bench and at the bedside. The fully revised 7th Edition of Cardiac Electrophysiology: From Cell to Bedside, by Drs. Douglas Zipes, Jose Jalife, and William Stevenson, provides the comprehensive, multidisciplinary coverage you need, including the underlying basic science and the latest clinical advances in the field. An attractive full-color design features color photos, tables, flow charts, ECGs, and more. All chapters have been significantly revised and updated by global leaders in the field, including 19 new chapters covering both basic and clinical topics. New topics include advances in basic science as well as recent clinical technology, such as leadless pacemakers; catheter ablation as a new class I recommendation for atrial fibrillation after failed medical therapy; current cardiac drugs and techniques; and a new video library covering topics that range from basic mapping (for the researcher) to clinical use (implantations). Each chapter is packed with the latest information necessary for optimal basic research as well as patient care, and additional figures, tables, and videos are readily available online. New editor William G. Stevenson, highly regarded in the EP community, brings a fresh perspective to this award-winning text. Expert Consult eBook version included with purchase. This enhanced eBook experience allows you to search all of the text, figures, images, videos (including video updates), glossary, and references from the book on a variety of devices.

Author: Luca Domenico D’Andrea
Publisher: Frontiers Media SA
ISBN: 2889718204
Category : Science
Languages : en
Pages : 135

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Author: Daniela Tropea
Publisher: Frontiers Media SA
ISBN: 2889453804
Category :
Languages : en
Pages : 586

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Book Description
Brain disorders, including neurological and neuropsychiatric conditions, represent a challenge for public health systems and society at large. The limited knowledge of their biology hampers the development of diagnostic tools and effective therapeutics. A clear understanding of the mechanisms that underlie the onset and progression of brain disorders is required in order to identify new avenues for therapeutic intervention. Overlapping genetic risk factors across different brain disorders suggest common linkages and pathophysiological mechanisms that underlie brain disorders. Methodological and technological advances are leading to new insights that go beyond traditional hypotheses. Taking account of underlying molecular, cellular and systems biology underlying brain function will play an important role in the classification of brain disorders in future. In this Research Topic, the latest advances in our understanding of biological mechanisms across different brain disorders are presented. The areas covered include developments in neurogenetics, epigenetics, plasticity, glial cell biology, neuroimmune interactions and new technologies associated with the study of brain function. Examples of how understanding of biological mechanisms are translating into research strategies that aim to advance diagnoses and treatment of brain disorders are discussed.

Author: Mohamed Chahine
Publisher: Springer
ISBN: 3319902849
Category : Medical
Languages : en
Pages : 448

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Book Description
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.