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Medientyp:
E-Artikel
Titel:
Role of the α1G T-Type Calcium Channel in Spontaneous Absence Seizures in Mutant Mice
Beteiligte:
Song, Inseon;
Kim, Daesoo;
Choi, Soonwook;
Sun, Minjeong;
Kim, Yeongin;
Shin, Hee-Sup
Erschienen:
Society for Neuroscience, 2004
Erschienen in:
The Journal of Neuroscience, 24 (2004) 22, Seite 5249-5257
Sprache:
Englisch
DOI:
10.1523/jneurosci.5546-03.2004
ISSN:
1529-2401;
0270-6474
Entstehung:
Anmerkungen:
Beschreibung:
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 α1A subunits of P/Q-type channels (α1A–/–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+currentsin vitro. To examine the role of increased T-currents in α1A–/–TC neurons, we cross-bred α1A–/–mice with mice harboring a null mutation for the gene encoding α1G, a major isotype of T-type Ca2+channels in TC neurons. α1A–/–/α1G–/–mice showed a complete loss of T-type Ca2+currents in TC neurons and displayed no SWDs. Interestingly, α1A–/–/α1G+/–mice had 75% of the T-type Ca2+currents in TC neurons observed in α1A+/+/α1G+/+mice and showed SWD activity that was quantitatively similar to that in α1A–/–/α1G+/+mice. Similar results were obtained using double-mutant mice harboring the α1G mutation plus another mutation also used as a model for absence seizures, i.e.,lethargic(β4lh/lh),tottering(α1Atg/tg), orstargazer(γ2stg/stg). The present results reveal that α1G 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.