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.
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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 |
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