Abstract
Electrogenesis of efficiently propagated action potentials requires synchronized opening of transmembrane Na+ channels possessing a sodium selectivity-filter, a high-throughput ion-conductance pathway, and voltage-dependent gating functions. These properties of the Na+ channel have long been the target of molecular analysis. Several toxins and drugs, known to selectively bind to Na + channels, have been used as pharmacological tools to investigate Na+ channel properties either electrophysiologically or chemically. Recent analyses of the protein crystal structure of bacterial voltage-dependent K+ channels have provided important clues to the identity of mobile structures involved in channel gating. The new information may be applicable to Na+ channels, and may well require a total revision of our understanding of gating mechanisms of sodium channels. Several experiments challenge the emerging view that channel gating by S6 transmembrane segments is triggered by signals from voltage sensors floating in membrane lipid. Herein, we review the various toxin and drug molecules that affect the gating behavior of Na+ channels in this new structural framework, by characterizing the binding sites of these toxins, and assessing the pharmacological effects resulting from changes in the structure of the toxin or sodium channel.
Keywords: inactivation gate, Membrane depolarization, Tetrodotoxin, Methanethiosulfonate, Myocytes
Current Pharmaceutical Design
Title: Na+ Channel Pharmacology and Molecular Mechanisms of Gating
Volume: 12 Issue: 4
Author(s): K. Yamaoka, S. M. Vogel and I. Seyama
Affiliation:
Keywords: inactivation gate, Membrane depolarization, Tetrodotoxin, Methanethiosulfonate, Myocytes
Abstract: Electrogenesis of efficiently propagated action potentials requires synchronized opening of transmembrane Na+ channels possessing a sodium selectivity-filter, a high-throughput ion-conductance pathway, and voltage-dependent gating functions. These properties of the Na+ channel have long been the target of molecular analysis. Several toxins and drugs, known to selectively bind to Na + channels, have been used as pharmacological tools to investigate Na+ channel properties either electrophysiologically or chemically. Recent analyses of the protein crystal structure of bacterial voltage-dependent K+ channels have provided important clues to the identity of mobile structures involved in channel gating. The new information may be applicable to Na+ channels, and may well require a total revision of our understanding of gating mechanisms of sodium channels. Several experiments challenge the emerging view that channel gating by S6 transmembrane segments is triggered by signals from voltage sensors floating in membrane lipid. Herein, we review the various toxin and drug molecules that affect the gating behavior of Na+ channels in this new structural framework, by characterizing the binding sites of these toxins, and assessing the pharmacological effects resulting from changes in the structure of the toxin or sodium channel.
Export Options
About this article
Cite this article as:
Yamaoka K., Vogel M. S. and Seyama I., Na+ Channel Pharmacology and Molecular Mechanisms of Gating, Current Pharmaceutical Design 2006; 12 (4) . https://dx.doi.org/10.2174/138161206775474468
DOI https://dx.doi.org/10.2174/138161206775474468 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
GABA System as a Target for New Drugs
Current Medicinal Chemistry Editorial (Thematic Issue: GABAergic Modulation as Treatment Strategy: Consideration of Several Diseases)
Current Pharmaceutical Design 5'-Nucleotidases, Nucleosides and their Distribution in the Brain: Pathological and Therapeutic Implications
Current Medicinal Chemistry Herbal Compounds with Special Reference to Gastrodin as Potential Therapeutic Agents for Microglia Mediated Neuroinflammation
Current Medicinal Chemistry Bipolar Affective Disorder, Epilepsy and Migraine – Does Possible Shared Pathogenesis Explain their Association?
Current Psychopharmacology Autoimmunity and Frontotemporal Dementia
Current Alzheimer Research Pedunculopontine Nucleus Stimulation in Intractable Epilepsy: A Recent Patent on Deep Brain Stimulation Therapy
Recent Patents and Topics on Imaging (Discontinued) PET Radioligands for In Vivo Visualization of Neuroinflammation
Current Pharmaceutical Design GluN2B/N-methyl-D-aspartate Receptor Antagonists: Advances in Design, Synthesis, and Pharmacological Evaluation Studies
CNS & Neurological Disorders - Drug Targets Biological Activities of Quinoline Derivatives
Mini-Reviews in Medicinal Chemistry Role of the α7 Nicotinic Acetylcholine Receptor and RIC-3 in the Cholinergic Anti-inflammatory Pathway
Central Nervous System Agents in Medicinal Chemistry Valproic Acid in the Complex Therapy of Malignant Tumors
Current Drug Targets Anxiety: A Systematic Review of Neurobiology, Traditional Pharmaceuticals and Novel Alternatives from Medicinal Plants
CNS & Neurological Disorders - Drug Targets Aptamers as Tools to Study Dysfunction in the Neuronal System
Current Medicinal Chemistry - Central Nervous System Agents Quinoline Derivatives: Candidate Drugs for a Class B G-Protein Coupled Receptor, the Calcitonin Gene-Related Peptide Receptor, a Cause of Migraines
CNS & Neurological Disorders - Drug Targets Toxins Targeting Voltage-Activated Ca<sup>2+</sup> Channels and their Potential Biomedical Applications
Current Topics in Medicinal Chemistry Therapeutic Role of Zonisamide in Neuropsychiatric Disorders
Mini-Reviews in Medicinal Chemistry Diabetes Gene Therapy: Potential and Challenges
Current Gene Therapy Metabotropic Glutamate Receptor 5 in Down's Syndrome Hippocampus During Development: Increased Expression in Astrocytes
Current Alzheimer Research Effect of Levetiracetam on Cognitive Function and Clonic Seizure Frequency in Children with Epilepsy
Current Molecular Medicine