Abstract
Idiopathic epilepsies are genetically determined diseases of the central nervous system characterized by typical epileptic seizures and EEG abnormalities but not associated with structural brain lesions. In recent years, an increasing number of mutations associated with idiopathic epilepsy syndromes were identified in genes encoding subunits of voltageor ligand-gated ion channels. These encouraging results provide a plausible pathophysiological concept, since ion channels form the basis for neuronal excitability and are the major targets for anticonvulsive pharmacotherapy. The first epilepsy genes were identified for rare autosomal dominant syndromes within large pedigrees. Recently, a few mutations were also found for the frequent classical forms of idiopathic generalized epilepsies (IGE), for example absence or juvenile myoclonic epilepsy. The mutations can affect ion channels which on one hand have been known since several decades to be crucial for neuronal function, such as the voltage-gated sodium channel or the GABAA receptor, or on the other hand were newly identified within the last decade as KCNQ potassium channels or the ClC-2 chloride channel. Functional studies characterizing the molecular defects of the mutant channels point to a central role of GABAergic synaptic inhibition in the pathophysiology of IGE. Furthermore, newly discovered genes may be suitable as novel targets for pharmacotherapy such as KCNQ channels for the anticonvulsant drug retigabine. Altogether, these genetic and pathophysiological investigations will enhance our knowledge about the understanding of epileptogenesis and can help to improve anticonvulsive therapy.
Keywords: Ion channel, epilepsy, genetics, electrophysiology, patch clamp
Current Pharmaceutical Design
Title: Ion Channel Defects in Idiopathic Epilepsies
Volume: 11 Issue: 21
Author(s): Holger Lerche, Yvonne G. Weber, Karin Jurkat-Rott and Frank Lehmann-Horn
Affiliation:
Keywords: Ion channel, epilepsy, genetics, electrophysiology, patch clamp
Abstract: Idiopathic epilepsies are genetically determined diseases of the central nervous system characterized by typical epileptic seizures and EEG abnormalities but not associated with structural brain lesions. In recent years, an increasing number of mutations associated with idiopathic epilepsy syndromes were identified in genes encoding subunits of voltageor ligand-gated ion channels. These encouraging results provide a plausible pathophysiological concept, since ion channels form the basis for neuronal excitability and are the major targets for anticonvulsive pharmacotherapy. The first epilepsy genes were identified for rare autosomal dominant syndromes within large pedigrees. Recently, a few mutations were also found for the frequent classical forms of idiopathic generalized epilepsies (IGE), for example absence or juvenile myoclonic epilepsy. The mutations can affect ion channels which on one hand have been known since several decades to be crucial for neuronal function, such as the voltage-gated sodium channel or the GABAA receptor, or on the other hand were newly identified within the last decade as KCNQ potassium channels or the ClC-2 chloride channel. Functional studies characterizing the molecular defects of the mutant channels point to a central role of GABAergic synaptic inhibition in the pathophysiology of IGE. Furthermore, newly discovered genes may be suitable as novel targets for pharmacotherapy such as KCNQ channels for the anticonvulsant drug retigabine. Altogether, these genetic and pathophysiological investigations will enhance our knowledge about the understanding of epileptogenesis and can help to improve anticonvulsive therapy.
Export Options
About this article
Cite this article as:
Lerche Holger, Weber G. Yvonne, Jurkat-Rott Karin and Lehmann-Horn Frank, Ion Channel Defects in Idiopathic Epilepsies, Current Pharmaceutical Design 2005; 11 (21) . https://dx.doi.org/10.2174/1381612054546815
DOI https://dx.doi.org/10.2174/1381612054546815 |
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
-
Relationship Between Oxidative Stress, Tau Level and Antioxidant Mechanisms of the KEAP-1/NRF-2/HO-1 in Children with Hydrocephalus
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Current Clinical Applications of In Vivo Magnetic Resonance Spectroscopy and Spectroscopic Imaging
Current Medical Imaging Therapeutic Role of Synaptic Vesicle Glycoprotein 2A (SV2A) in Modulating Epileptogenesis
CNS & Neurological Disorders - Drug Targets Persistent Current Blockers of Voltage-Gated Sodium Channels: A Clinical Opportunity for Controlling Metastatic Disease
Recent Patents on Anti-Cancer Drug Discovery Pharmacological Manipulation of Neural Progenitor Pathways In Situ: Possibilities for Neural Restoration in the Injured Adult Brain
Current Medicinal Chemistry - Central Nervous System Agents Considerations in the Development of Reversibly Binding PET Radioligands for Brain Imaging
Current Medicinal Chemistry Positive Allosteric Modulators of the Metabotropic Glutamate Receptor Subtype 2 (mGluR2)
Current Topics in Medicinal Chemistry Patent Selections
Recent Patents on DNA & Gene Sequences Histamine and Histamine Receptor Antagonists in Cancer Biology
Inflammation & Allergy - Drug Targets (Discontinued) Erythropoietin: A Neuroprotective Agent in Cerebral Hypoxia, Neurodegeneration, and Epilepsy
Current Pharmaceutical Design Novel Kynurenic Acid Analogues in the Treatment of Migraine and Neurodegenerative Disorders: Preclinical Studies and Pharmaceutical Design
Current Pharmaceutical Design Epigenetic Modification in Neuropathic Pain
Current Pharmaceutical Design Neurophysiological Alterations in the Prepsychotic Phases
Current Pharmaceutical Design Synthesis and Evaluation of Anticonvulsant Activity of Some N-[(4-Chlor- 2-methylphenoxy)ethyl]- and N-[(4-Chlor-2-methylphenoxy)acetyl]aminoalkanols
Letters in Drug Design & Discovery Unmasking Sex-Based Disparity in Neuronal Metabolism
Current Pharmaceutical Design Syncope: Review of Monitoring Modalities
Current Cardiology Reviews The Microbial Quality Aspects and Decontamination Approaches for the Herbal Medicinal Plants and Products: An in-Depth Review
Current Pharmaceutical Design Dietary Approaches and Supplements in the Prevention of Cognitive Decline and Alzheimer's Disease
Current Pharmaceutical Design HIV-1 Reactivation Induced by Apicidin Involves Histone Modification in Latently Infected Cells
Current HIV Research Tackling the Elusive Challenges Relevant to Conquering the 100-Plus Year Old Problem of Alzheimer’s Disease
Current Alzheimer Research