Abstract
T-type calcium channels open in response to small depolarizations of the plasma membrane. The entry of two positive charges with every calcium ion leads to a further depolarization of the membrane, the low threshold spike, and opening of channels that have a higher threshold. In this manner, T-channels play an important pacemaker role in gating the activity of Na+ and Ca2+ channels. T-channels are preferentially expressed in dendrites, suggesting they play important roles in synaptic integration. Pharmacological evidence indicates that they are expressed in the receptive fields of sensory neurons, suggesting they play a primary role in nociception. Molecular cloning of the three T-channel genes has allowed detailed studies on their channel properties, pharmacology, distribution in the brain, up-regulation in animal models of disease, and provided the tools to screen for novel drugs. Studies on transgenic animals have provided the proof-ofconcept that T-channels are important drug targets for the treatment of absence epilepsy and neuropathic pain. Mutations in ion channel genes, or channelopathies, have been found in many diseases. Similarly, T-channel gene mutations have been found in patients with childhood absence epilepsy. Considering the important role T-channels play in the thalamus, it is likely that T-channel mutations also contribute to a wider range of disorders characterized by thalamocortical dysrhythmia.
Keywords: Calcium Channels, Cloning, Electrophysiology, Ion Channel Gating, Mutation, Human, Child, Absence, Genetics, Physiopathology
Current Pharmaceutical Design
Title: The Role of T-Type Calcium Channels in Epilepsy and Pain
Volume: 12 Issue: 18
Author(s): M. T. Nelson, S. M. Todorovic and E. Perez-Reyes
Affiliation:
Keywords: Calcium Channels, Cloning, Electrophysiology, Ion Channel Gating, Mutation, Human, Child, Absence, Genetics, Physiopathology
Abstract: T-type calcium channels open in response to small depolarizations of the plasma membrane. The entry of two positive charges with every calcium ion leads to a further depolarization of the membrane, the low threshold spike, and opening of channels that have a higher threshold. In this manner, T-channels play an important pacemaker role in gating the activity of Na+ and Ca2+ channels. T-channels are preferentially expressed in dendrites, suggesting they play important roles in synaptic integration. Pharmacological evidence indicates that they are expressed in the receptive fields of sensory neurons, suggesting they play a primary role in nociception. Molecular cloning of the three T-channel genes has allowed detailed studies on their channel properties, pharmacology, distribution in the brain, up-regulation in animal models of disease, and provided the tools to screen for novel drugs. Studies on transgenic animals have provided the proof-ofconcept that T-channels are important drug targets for the treatment of absence epilepsy and neuropathic pain. Mutations in ion channel genes, or channelopathies, have been found in many diseases. Similarly, T-channel gene mutations have been found in patients with childhood absence epilepsy. Considering the important role T-channels play in the thalamus, it is likely that T-channel mutations also contribute to a wider range of disorders characterized by thalamocortical dysrhythmia.
Export Options
About this article
Cite this article as:
Nelson T. M., Todorovic M. S. and Perez-Reyes E., The Role of T-Type Calcium Channels in Epilepsy and Pain, Current Pharmaceutical Design 2006; 12 (18) . https://dx.doi.org/10.2174/138161206777585184
DOI https://dx.doi.org/10.2174/138161206777585184 |
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
-
Endocrine Abnormalities Induced by Antiepileptic Drugs
Current Pediatric Reviews Concerns with AED Conversion: Comparison of Patient and Physician Perspectives
Current Neuropharmacology Hallucinations Associated with Topiramate Therapy: A Case Report and Review of the Literature
Current Drug Safety Diagnostic Approach to Mitochondrial Disorders: the Need for a Reliable Biomarker
Current Molecular Medicine Psychoemotional Background of Temporomandibular Joint Dysfunction and Possible Drug Therapy
Letters in Drug Design & Discovery Fused Azolo-Quinoxalines: Candidates for Medicinal Chemistry. A Review of their Biological Applications
Current Medicinal Chemistry Tandem Mass Spectrometry Newborn Screening for Inborn Errors of Intermediary Metabolism: Abnormal Profile Interpretation
Current Medicinal Chemistry Targeting Chromatin Remodeling to Prevent Cardiovascular Disease in Diabetes
Current Pharmaceutical Biotechnology The GABAergic System and the Gastrointestinal Physiopathology
Current Pharmaceutical Design Metabotropic Glutamate Receptors in the Control of Mood Disorders
CNS & Neurological Disorders - Drug Targets Differences in Relative Levels of 88 microRNAs in Various Regions of the Normal Adult Human Brain
MicroRNA Synthesis, Anticonvulsant and Binding Interaction Study of Novel Piperamides with Bovine Serum Albumin by Fluorescence Spectroscopy
Central Nervous System Agents in Medicinal Chemistry Pathogenesis, Experimental Models and Contemporary Pharmacotherapy of Irritable Bowel Syndrome: Story About the Brain-Gut Axis
Current Neuropharmacology Polycystic Ovary Syndrome as a Proinflammatory State: The Role of Adipokines
Current Pharmaceutical Design Disruption of Circadian Rhythms and Delirium, Sleep Impairment and Sepsis in Critically ill Patients. Potential Therapeutic Implications for Increased Light-Dark Contrast and Melatonin Therapy in an ICU Environment
Current Pharmaceutical Design A Multi-Functional Organelle Mitochondrion is Involved in Cell Death, Proliferation and Disease
Current Medicinal Chemistry Integrated Analysis on the Physicochemical Properties of Dihydropyridine Calcium Channel Blockers in Grapefruit Juice Interactions
Current Pharmaceutical Biotechnology Editorial [Hot Topic: PET and SPECT in Drug Evaluation and Drug Design Imaging Inflammatory Processes, Tumors, and the Endocannabinoid System(Executive Editor: Aren van Waarde)]
Current Pharmaceutical Design Development and Validation of 'Level A' In Vitro - In Vivo Correlation for Extended Release Tablets of Lamotrigine
Current Bioactive Compounds Ultra-micronized Palmitoylethanolamide: An Efficacious Adjuvant Therapy for Parkinson’s Disease
CNS & Neurological Disorders - Drug Targets