Sodium Channels and Neuronal Hyperexcitability

Sodium Channels and Neuronal Hyperexcitability PDF 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.

Sodium Channels and Neuronal Hyperexcitability

Sodium Channels and Neuronal Hyperexcitability PDF 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.

Voltage Gated Sodium Channels

Voltage Gated Sodium Channels PDF 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.

The Modulation of Voltage-gated Sodium Channels and Neuronal Excitability by FGF14

The Modulation of Voltage-gated Sodium Channels and Neuronal Excitability by FGF14 PDF Author: Junyang Lou
Publisher:
ISBN:
Category :
Languages : en
Pages : 240

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Book Description


Sodium Channels, Pain, and Analgesia

Sodium Channels, Pain, and Analgesia PDF Author: Kevin Coward
Publisher: Springer Science & Business Media
ISBN: 376437411X
Category : Medical
Languages : en
Pages : 204

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Book Description
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.

Jasper's Basic Mechanisms of the Epilepsies

Jasper's Basic Mechanisms of the Epilepsies PDF Author: Jeffrey Noebels
Publisher: OUP USA
ISBN: 0199746540
Category : Medical
Languages : en
Pages : 1258

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Book Description
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.

Ion Channels in Epilepsy

Ion Channels in Epilepsy PDF Author: Jie Tao
Publisher:
ISBN:
Category : Electronic books
Languages : en
Pages : 0

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Book Description
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.

The Oxford Handbook of Neuronal Ion Channels

The Oxford Handbook of Neuronal Ion Channels PDF Author: Arin Bhattacharjee
Publisher: Oxford University Press
ISBN: 0190669160
Category :
Languages : en
Pages : 785

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Book Description
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. The book explains how ion channels open and close, how they can be selective for specific ions, and how they give rise to action potentials. Included are in-depth chapters discussing specific classes of ion channels: potassium channels, sodium channels, neurotransmitter-gated ion channels and other specialized channels. Throughout the handbook, important insight is provided on the contribution ion channels make to neuronal excitability and to synaptic transmission. The handbook goes further to discuss channelopathies, a group of human diseases such as epilepsy, pain and migraines that can be caused by ion channel dysfunction. For neuroscientists, biophysicists and neuropharmacologists, this handbook is a valuable reference of ion channel biology and function.

CaMKII Phosphorylation of the Voltage-gated Sodium Channel Nav1.6 Regulates Channel Function and Neuronal Excitability

CaMKII Phosphorylation of the Voltage-gated Sodium Channel Nav1.6 Regulates Channel Function and Neuronal Excitability PDF 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.

Epilepsy

Epilepsy PDF Author: Isam Jaber Al-Zwaini
Publisher: BoD – Books on Demand
ISBN: 1789238676
Category : Medical
Languages : en
Pages : 221

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Book Description
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.

The Contribution of the Sodium Channel Subunit Na_1tnv1.6 to Neuronal Excitability

The Contribution of the Sodium Channel Subunit Na_1tnv1.6 to Neuronal Excitability PDF Author: Michael Winfried Royeck
Publisher:
ISBN:
Category :
Languages : en
Pages : 160

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Book Description