TY - JOUR T1 - Role of the α1G T-Type Calcium Channel in Spontaneous Absence Seizures in Mutant Mice JF - The Journal of Neuroscience JO - J. Neurosci. SP - 5249 LP - 5257 DO - 10.1523/JNEUROSCI.5546-03.2004 VL - 24 IS - 22 AU - Inseon Song AU - Daesoo Kim AU - Soonwook Choi AU - Minjeong Sun AU - Yeongin Kim AU - Hee-Sup Shin Y1 - 2004/06/02 UR - http://www.jneurosci.org/content/24/22/5249.abstract N2 - 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+ currents in 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), or stargazer (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. ER -