Source:http://linkedlifedata.com/resource/pubmed/id/15175395
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
22
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| pubmed:dateCreated |
2004-6-3
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| pubmed:abstractText |
Alterations in thalamic T-type Ca2+ channels are thought to contribute to the pathogenesis of absence seizures. Here, we found that mice with a null mutation for the pore-forming alpha1A subunits of P/Q-type channels (alpha1A-/- mice) were prone to absence seizures characterized by typical spike-and-wave discharges (SWDs) and behavioral arrests. Isolated thalamocortical relay (TC) neurons from these mice showed increased T-type Ca2+ currents in vitro. To examine the role of increased T-currents in alpha1A-/- TC neurons, we cross-bred alpha1A-/- mice with mice harboring a null mutation for the gene encoding alpha1G, a major isotype of T-type Ca2+ channels in TC neurons. alpha1A-/-/alpha1G-/- mice showed a complete loss of T-type Ca2+ currents in TC neurons and displayed no SWDs. Interestingly, alpha1A-/-/alpha1G+/- mice had 75% of the T-type Ca2+ currents in TC neurons observed in alpha1A+/+/alpha1G+/+ mice and showed SWD activity that was quantitatively similar to that in alpha1A-/-/alpha1G+/+ mice. Similar results were obtained using double-mutant mice harboring the alpha1G mutation plus another mutation also used as a model for absence seizures, i.e., lethargic (beta4(lh/lh)), tottering (alpha1A(tg/tg)), or stargazer (gamma2(stg/stg)). The present results reveal that alpha1G T-type Ca2+ channels play a critical role in the genesis of spontaneous absence seizures resulting from hypofunctioning P/Q-type channels, but that the augmentation of thalamic T-type Ca2+ currents is not an essential step in the genesis of absence seizures.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels, N-Type,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels, T-Type,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Subunits,
http://linkedlifedata.com/resource/pubmed/chemical/voltage-dependent calcium channel...
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
1529-2401
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
2
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| pubmed:volume |
24
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
5249-57
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:15175395-Animals,
pubmed-meshheading:15175395-Calcium,
pubmed-meshheading:15175395-Calcium Channels, N-Type,
pubmed-meshheading:15175395-Calcium Channels, T-Type,
pubmed-meshheading:15175395-Cell Separation,
pubmed-meshheading:15175395-Cerebral Cortex,
pubmed-meshheading:15175395-Crosses, Genetic,
pubmed-meshheading:15175395-Disease Models, Animal,
pubmed-meshheading:15175395-Disease Progression,
pubmed-meshheading:15175395-Electrodes, Implanted,
pubmed-meshheading:15175395-Electroencephalography,
pubmed-meshheading:15175395-Epilepsy, Absence,
pubmed-meshheading:15175395-Mice,
pubmed-meshheading:15175395-Mice, Neurologic Mutants,
pubmed-meshheading:15175395-Mutation,
pubmed-meshheading:15175395-Neural Pathways,
pubmed-meshheading:15175395-Neurons,
pubmed-meshheading:15175395-Patch-Clamp Techniques,
pubmed-meshheading:15175395-Protein Subunits,
pubmed-meshheading:15175395-Thalamus
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| pubmed:year |
2004
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| pubmed:articleTitle |
Role of the alpha1G T-type calcium channel in spontaneous absence seizures in mutant mice.
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| pubmed:affiliation |
Center for Calcium and Learning, Korea Institute of Science and Technology, Cheongryang, Seoul, 136-791, Korea.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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