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Sodium Channels And Neuronal Hyperexcitability
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Book Synopsis Sodium Channels and Neuronal Hyperexcitability by : Gregory R. Bock
Download or read book Sodium Channels and Neuronal Hyperexcitability written by Gregory R. Bock and published by John Wiley & Sons. This book was released on 2001-12-21 with total page 258 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Book Synopsis The Modulation of Voltage-gated Sodium Channels and Neuronal Excitability by FGF14 by : Junyang Lou
Download or read book The Modulation of Voltage-gated Sodium Channels and Neuronal Excitability by FGF14 written by Junyang Lou and published by . This book was released on 2006 with total page 240 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Sodium Channels, Pain, and Analgesia by : Kevin Coward
Download or read book Sodium Channels, Pain, and Analgesia written by Kevin Coward and published by Springer Science & Business Media. This book was released on 2006-01-17 with total page 204 pages. Available in PDF, EPUB and Kindle. Book excerpt: Sodium channels confer excitability on neurons in nociceptive pathways and exhibit neuronal tissue specific and injury regulated expression. This volume provides recent insights into the control of expression, functioning and membrane trafficking of nervous system sodium channels and reviews why sodium channel sub-types are potentially important drug targets in the treatment of pain. The roles of sodium channels in dental and visceral pain are also addressed. The emerging role of sodium channel Nav1.3 in neuropathic states is another important theme. Authors from the pharmaceutical industry discuss pharmacological approaches to the drug targeting of sodium channels, and in particular Nav1.8, exclusively expressed in nociceptive neurons. The final chapter highlights the functional diversity of sodium channels in part provided by post-transcriptional processing and the insights into sodium channel function that are being provided by tissue specific and inducible gene knock-out technology.
Book Synopsis Voltage Gated Sodium Channels by : Peter C. Ruben
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.
Book Synopsis Jasper's Basic Mechanisms of the Epilepsies by : Jeffrey Noebels
Download or read book Jasper's Basic Mechanisms of the Epilepsies written by Jeffrey Noebels and published by OUP USA. This book was released on 2012-06-29 with total page 1258 pages. Available in PDF, EPUB and Kindle. Book excerpt: Jasper's Basic Mechanisms, Fourth Edition, is the newest most ambitious and now clinically relevant publishing project to build on the four-decade legacy of the Jasper's series. In keeping with the original goal of searching for "a better understanding of the epilepsies and rational methods of prevention and treatment.", the book represents an encyclopedic compendium neurobiological mechanisms of seizures, epileptogenesis, epilepsy genetics and comordid conditions. Of practical importance to the clinician, and new to this edition are disease mechanisms of genetic epilepsies and therapeutic approaches, ranging from novel antiepileptic drug targets to cell and gene therapies.
Book Synopsis Ion Channels in Epilepsy by : Jie Tao
Download or read book Ion Channels in Epilepsy written by Jie Tao and published by . This book was released on 2019 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Voltage-gated ion channels (VGICs), extensively distributed in the central nervous system (CNS), are responsible for the generation as well as modulation of neuroexcitability and considered as vital players in the pathogenesis of human epilepsy, with regulating the shape and duration of action potentials (APs). For instance, genetic alterations or abnormal expression of voltage-gated sodium channels (VGSCs), Kv channels, and voltage-gated calcium channels (VGCCs) are proved to be associated with epileptogenesis. This chapter aims to highlight recent discoveries on the mutations in VGIC genes and dysfunction of VGICs in epilepsy, especially focusing on the pathophysiological and pharmacological properties. Understanding the role of epilepsy-associated VGICs might not only contribute to clarify the mechanism of epileptogenesis and genetic modifiers but also provide potential targets for the precise treatment of epilepsy.
Book Synopsis CaMKII Phosphorylation of the Voltage-gated Sodium Channel Nav1.6 Regulates Channel Function and Neuronal Excitability by : Agnes Sara Zybura
Download or read book CaMKII Phosphorylation of the Voltage-gated Sodium Channel Nav1.6 Regulates Channel Function and Neuronal Excitability written by Agnes Sara Zybura and published by . This book was released on 2021 with total page 622 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Epilepsy written by Isam Jaber Al-Zwaini and published by BoD – Books on Demand. This book was released on 2019-11-13 with total page 221 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epilepsy is the most common neurological disorder globally, affecting approximately 50 million people of all ages. It is one of the oldest diseases described in literature from remote ancient civilizations 2000-3000 years ago. Despite its long history and wide spread, epilepsy is still surrounded by myth and prejudice, which can only be overcome with great difficulty. The term epilepsy is derived from the Greek verb epilambanein, which by itself means to be seized and to be overwhelmed by surprise or attack. Therefore, epilepsy is a condition of getting over, seized, or attacked. The twelve very interesting chapters of this book cover various aspects of epileptology from the history and milestones of epilepsy as a disease entity, to the most recent advances in understanding and diagnosing epilepsy.
Book Synopsis The Contribution of the Sodium Channel Subunit Na_1tnv1.6 to Neuronal Excitability by : Michael Winfried Royeck
Download or read book The Contribution of the Sodium Channel Subunit Na_1tnv1.6 to Neuronal Excitability written by Michael Winfried Royeck and published by . This book was released on 2010 with total page 160 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Voltage-gated Sodium Channel Nav1.6 S-Palmitoylation Regulates Channel Functions and Neuronal Excitability by : Yanling Pan
Download or read book Voltage-gated Sodium Channel Nav1.6 S-Palmitoylation Regulates Channel Functions and Neuronal Excitability written by Yanling Pan and published by . This book was released on 2020 with total page 354 pages. Available in PDF, EPUB and Kindle. Book excerpt: The voltage-gated sodium channels (VGSCs) are critical determinants of neuronal excitability. They set the threshold for action potential generation. The VGSC isoform Nav1.6 participates in various physiological processes and contributes to distinct pathological conditions, but how Nav1.6 function is differentially regulated in different cell types and subcellular locations is not clearly understood. Some VGSC isoforms are subject to S-palmitoylation and exhibit altered functional properties in different S-palmitoylation states. This dissertation investigates the role of S-palmitoylation in Nav1.6 regulation and explores the consequences of S-palmitoylation in modulating neuronal excitability in physiological and pathological conditions. The aims of this dissertation were to 1) provide biochemical and electrophysiological evidence of Nav1.6 regulation by S-palmitoylation and identify specific S-palmitoylation sites in Nav1.6 that are important for excitability modulation, 2) determine the biophysical consequences of epilepsy-associated mutations in Nav1.6 and employ computational models for excitability prediction and 3) test the modulating effects of S-palmitoylation on aberrant Nav1.6 activity incurred by epilepsy mutations. To address these aims, an acyl-biotin exchange assay was used for Spalmitoylation detection and whole-cell electrophysiology was used for channel characterization and excitability examination. The results demonstrate that 1) Nav1.6 is biochemically modified and functionally regulated by S-palmitoylation in an isoform- and site-specific manner and altered S-palmitoylation status of the channel results in substantial changes of neuronal excitability, 2) epilepsy associated Nav1.6 mutations affect different aspects of channel function, but may all converge to gain-of-function alterations with enhanced resurgent currents and increased neuronal excitability and 3) S-palmitoylation can target specific Nav1.6 properties and could possibly be used to rescue abnormal channel function in diseased conditions. Overall, this dissertation reveals S-palmitoylation as a new mechanism for Nav1.6 regulation. This knowledge is critical for understanding the potential role of S-palmitoylation in isoform-specific regulation for VGSCs and providing potential targets for the modulation of excitability disorders.
Download or read book Ion Channel Diseases written by and published by Academic Press. This book was released on 2011-09-06 with total page 168 pages. Available in PDF, EPUB and Kindle. Book excerpt: Ion channel dysfunction in humans leads to impairment of the excitable processes necessary for the normal function of several tissues, such as muscle and brain. It follows that an increasing number of human diseases have been associated with malfunctioning ion channels, many of which have a genetic component. This volume of Advances in Genetics presents a broad and comprehensive overview of the inherited channelopathies in humans, including clinical, genetic and molecular aspects of these conditions. Keeping true to the scope of the serial, novel genomic and modeling research approaches and a review of potential therapeutic approaches for each of these conditions are also incorporated.
Book Synopsis NLF-1 Delivers a Sodium Leak Channel to Regulate Neuronal Excitability and Modulate Rhythmic Locomotion by : Lin Xie
Download or read book NLF-1 Delivers a Sodium Leak Channel to Regulate Neuronal Excitability and Modulate Rhythmic Locomotion written by Lin Xie and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis The> Contribution of the Sodium Channel Subunit Na V 1.6 to Neuronal Excitability by : Michael Winfried Royeck
Download or read book The> Contribution of the Sodium Channel Subunit Na V 1.6 to Neuronal Excitability written by Michael Winfried Royeck and published by . This book was released on 2010 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Seizures and Epilepsy by : Jerome Engel Jr
Download or read book Seizures and Epilepsy written by Jerome Engel Jr and published by Oxford University Press. This book was released on 2013-01-31 with total page 737 pages. Available in PDF, EPUB and Kindle. Book excerpt: This second edition of 'Seizures and Epilepsy' is completely revised, due to tremendous advances in the understanding of the fundamental neuronal mechanisms underlying epileptic phenomena, as well as current diagnosis and treatment, which have been heavily influenced over the past several decades by seminal neuroscientific developments, particularly the introduction of molecular neurobiology, genetics, and modern neuroimaging. This resource covers a broad range of both basic and clinical epileptology.
Book Synopsis Activity-dependent Plasticity of Neuronal Excitability by : Ingrid van Welie
Download or read book Activity-dependent Plasticity of Neuronal Excitability written by Ingrid van Welie and published by . This book was released on 2004 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Modulation of Sodium Activated Potassium Channels (KNa) by P38 MAP Kinase by : John Fleites
Download or read book Modulation of Sodium Activated Potassium Channels (KNa) by P38 MAP Kinase written by John Fleites and published by . This book was released on 2013 with total page 41 pages. Available in PDF, EPUB and Kindle. Book excerpt: Pain signaling is sensed by dorsal root ganglion (DRG) neurons. After nerve injury, DRG neurons can become hyperexcitable and generate a chronic and painful phenotype known as neuropathic pain. The exact underlying cellular mechanisms precipitating neuropathic pain are unclear, but altered ion channel properties are key in determining DRG neuronal hyperexcitability. One class of ion channels known as the sodium activated potassium (KNa) channels have been shown to regulate the resting membrane potential (RMP) and control firing accommodation in these neurons, and could very well be a central player in neuropathic pain. Multiple lines of evidence have indicated that p38 Mitogen Activated Protein Kinase (p38 MAPK) activity is important during neuropathic pain. Indeed, it has been recently shown that p38 MAPK facilitates neuronal regeneration after nerve crush of the sciatic nerve. Because of the roles of p38 MAPK in neuropathy and KNa channel involvement in DRG neuronal excitability, I sought to determine whether p38 MAPK regulates KNa channels in DRG neurons. I used anisomycin, a p38 MAPK activator, and a p38 MAPK Inhibitor to study the effects of p38 MAPK on potassium currents in rat embryonic DRG neurons and Slack KNa channels in heterologous expression systems. I show that KNa currents are upregulated by p38 MAPK in DRG neurons; Slack currents are also modulated by p38 MAPK. Using site-directed mutagenesis, I have shown that mutating one of Slack's putative p38 phosphorylation sites to glutamic acid significantly speeds up activation kinetics. These results suggest that KNa channels regulated by p38 MAPK in DRG neurons act to prevent hyperexcitability and may aid in the neuronal regeneration process after nerve injury.
Book Synopsis The Oxford Handbook of Neuronal Ion Channels by : Arin Bhattacharjee
Download or read book The Oxford Handbook of Neuronal Ion Channels written by Arin Bhattacharjee and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neurons are excitable cells. They use ions and electrical signaling to talk to each to other and when they talk to each other, neurons control behavior. The Oxford Handbook of Neuronal Ion Channels is an accessible reference describing the nature and properties of ion channels in neurons.
