Referenced in: none

Automatically associated channels: Cav2.1

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

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

Journal, date & volume: Biochem. Biophys. Res. Commun., 2015 Jul 17-24 , 463, 148-53

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26002462

Abstract
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 α1 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 α1 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 Ca(2+) 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.