Song, I Kim, D Choi, S Sun, M Kim, Y Shin, HS 2024-01-21T07:00:51Z 2024-01-21T07:00:51Z 2021-09-02 2004-06-02 0270-6474 https://pubs.kist.re.kr/handle/201004/137493 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(1h/1h)), 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. English SOC NEUROSCIENCE SPIKE-WAVE SYNAPTIC-TRANSMISSION ACTION-POTENTIALS THALAMIC NEURONS CA2+ CHANNELS N-TYPE CURRENTS MOUSE EPILEPSY MODEL Role of the alpha 1G T-type calcium channel in spontaneous absence seizures in mutant mice Article 10.1523/JNEUROSCI.5546-03.2004 1 JOURNAL OF NEUROSCIENCE, v.24, no.22, pp.5249 - 5257 JOURNAL OF NEUROSCIENCE 24 22 5249 5257 scie scopus 000221883100019 2-s2.0-2642523808 Neurosciences Neurosciences & Neurology Article SPIKE-WAVE SYNAPTIC-TRANSMISSION ACTION-POTENTIALS THALAMIC NEURONS CA2+ CHANNELS N-TYPE CURRENTS MOUSE EPILEPSY MODEL calcium Ca EEG electroencephalogram epilepsy gene mutant thalamus