Absence-like seizures and their pharmacological profile in tottering-6j mice

作者：Kim, Tae Yeon; Maki, Takehiro; Zhou, Ying; Sakai, Keita; Mizuno, Yuri; Ishikawa, Akiyoshi; Tanaka, Ryo; Niimi, Kimie; Li, Weidong; Nagano, Norihiro; Takahashi, Eiki^*

来源：Biochemical and Biophysical Research Communications, 2015, 463(1-2): 148-153.

DOI：10.1016/j.bbrc.2015.05.050

• Antiepileptic drug
• Ataxia
• Cacna1a
• Electroencephalograms
• Spike-and-wave discharge
• Tottering-6j mice

We previously showed that recessive ataxic tottering-6j mice carried a base substitution (C-to-A) in the consensus splice acceptor sequence linked to exon 5 of the alpha(1) subunit of the Cav2.1 channel gene (Cacna1a), resulting in the skipping of exon 5 and deletion of part of the S4-S5 linker, S5, and part of the S5-S6 linker in domain I of the alpha(1) subunit of the Cav2.1 channel. However, the electrophysiological and pharmacological consequences of this mutation have not previously been investigated. Upon whole-cell patch recording of the recombinant Cav2.1 channel in heterologous reconstitution expression systems, the mutant-type channel exhibited a lower recovery time after inactivation of Ca2 channel current, without any change in peak current density or the current-voltage relationship. Tottering-6j mice exhibited absence-like seizures, characterized by bilateral and synchronous 5-8 Hz spike-and-wave discharges on cortical and hippocampal electroencephalograms, concomitant with sudden immobility and staring. The pharmacological profile of the seizures was similar to that of human absence epilepsy; the seizures were inhibited by ethosuximide and valproic acid, but not by phenytoin. Thus, the tottering-6j mouse is a useful model for studying Cav2.1 channel functions and Cacna1a-related diseases, including absence epilepsy.

• 出版日期2015-7-17
• 单位上海交通大学; RIKEN