Abstract
Voltage-gated calcium channels are found in the plasma membrane of many excitable and non-excitable cells. When open, they permit influx of calcium, which acts as a second messenger to initiate diverse physiological cellular processes. Ten unique α 1 subunits, grouped in three families (CaV1, CaV2, and CaV3), encode biophysically and pharmacologically distinct low-voltage-activated T-type and high-voltage-activated L-type, N-type, P/Q-type, and R-type calcium channels. T-type calcium channels are found in neurons where they generate low-threshold calcium spikes and influence action potential firing patterns, in heart cells where they influence pacemaking and impulse conduction, in smooth muscle cells where they regulate myogenic tone and proliferation, in endocrine cells where they regulate hormone secretion, and in sperm where they regulate the acrosome reaction. Validation of T-type calcium channels in disease is based on an abundance of data pertaining to clinical efficacy of T-type calcium channel blockers in certain human conditions as well as information relating to the distribution, functional properties, and physiological roles of these channels. This review focuses on the cellular and molecular pharmacology of T-type calcium channels. It describes novel research approaches to discover potent and selective T-type calcium channel modulators as potential drugs for treating human disease and as tools for understanding better the physiological roles of T-type calcium channels.
Keywords: epilepsy, Mibefradil, Metal Cations, Peptide Toxins, Zonisamide
CNS & Neurological Disorders - Drug Targets
Title: Pharmacology and Drug Discovery for T-Type Calcium Channels
Volume: 5 Issue: 6
Author(s): Joseph G. McGivern
Affiliation:
Keywords: epilepsy, Mibefradil, Metal Cations, Peptide Toxins, Zonisamide
Abstract: Voltage-gated calcium channels are found in the plasma membrane of many excitable and non-excitable cells. When open, they permit influx of calcium, which acts as a second messenger to initiate diverse physiological cellular processes. Ten unique α 1 subunits, grouped in three families (CaV1, CaV2, and CaV3), encode biophysically and pharmacologically distinct low-voltage-activated T-type and high-voltage-activated L-type, N-type, P/Q-type, and R-type calcium channels. T-type calcium channels are found in neurons where they generate low-threshold calcium spikes and influence action potential firing patterns, in heart cells where they influence pacemaking and impulse conduction, in smooth muscle cells where they regulate myogenic tone and proliferation, in endocrine cells where they regulate hormone secretion, and in sperm where they regulate the acrosome reaction. Validation of T-type calcium channels in disease is based on an abundance of data pertaining to clinical efficacy of T-type calcium channel blockers in certain human conditions as well as information relating to the distribution, functional properties, and physiological roles of these channels. This review focuses on the cellular and molecular pharmacology of T-type calcium channels. It describes novel research approaches to discover potent and selective T-type calcium channel modulators as potential drugs for treating human disease and as tools for understanding better the physiological roles of T-type calcium channels.
Export Options
About this article
Cite this article as:
McGivern G. Joseph, Pharmacology and Drug Discovery for T-Type Calcium Channels, CNS & Neurological Disorders - Drug Targets 2006; 5 (6) . https://dx.doi.org/10.2174/187152706779025535
DOI https://dx.doi.org/10.2174/187152706779025535 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...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
Related Articles
-
Subject Index To Volume 2
Current Rheumatology Reviews Computational Methods in Determination of Pharmacophore Models of 5-HT<sub>1A</sub>, 5-HT<sub>2A</sub> and 5-HT<sub>7</sub> Receptors
Mini-Reviews in Medicinal Chemistry Src Family Kinases in the Central Nervous System: Their Emerging Role in Pathophysiology of Migraine and Neuropathic Pain
Current Neuropharmacology Epigenetic Effects Mediated by Antiepileptic Drugs and their Potential Application
Current Neuropharmacology Novel Pyrimidine based Semicarbazones: Confirmation of Four Binding Site Pharmacophoric Model Hypothesis for Antiepileptic Activity
Central Nervous System Agents in Medicinal Chemistry Editorial [Hot Topic: Monotherapy to Polytherapy: Antiepileptic Drug Conversions Through the Spectrum of Epilepsy Care (Guest Editor: Erik K. St. Louis)]
Current Neuropharmacology Adenosine Neuromodulation and Traumatic Brain Injury
Current Neuropharmacology PET Imaging in Clinical Drug Abuse Research
Current Pharmaceutical Design Human Microdialysis
Current Pharmaceutical Biotechnology UCLA’s Molecular Screening Shared Resource: Enhancing Small Molecule Discovery with Functional Genomics and New Technology
Combinatorial Chemistry & High Throughput Screening Pathogenesis and Subtype of Intracerebral Hemorrhage (ICH) and ICH Score Determines Prognosis
Current Neurovascular Research Antimicrobial Drug Interactions in the Critically Ill Patients
Current Clinical Pharmacology Adaptive Behavior in Williams-Beuren Syndrome, Down Syndrome, and Autism Spectrum Disorder
Current Psychiatry Reviews Brain-Delivery of Zinc-Ions as Potential Treatment for Neurological Diseases: Mini Review
Drug Delivery Letters Anticonvulsant Action and Long-term Effects of Gabapentin
Current Neuropharmacology Bioinformatic Screening of Autoimmune Disease Genes and Protein Structure Prediction with FAMS for Drug Discovery
Protein & Peptide Letters Positron Emission Tomography: Applications In Drug Discovery and Drug Development
Current Topics in Medicinal Chemistry Computational Drug Repositioning: A Lateral Approach to Traditional Drug Discovery?
Current Topics in Medicinal Chemistry Osteoporotic Fracture Healing: Potential Use of Medicinal Plants from the Tropics
Current Drug Targets Congenital Cytomegalovirus Prevention, Awareness and Policy Recommendations - A Scoping Study
Infectious Disorders - Drug Targets