| First Author | Kim TY | Year | 2015 |
| Journal | Biochem Biophys Res Commun | Volume | 463 |
| Issue | 1-2 | Pages | 148-53 |
| PubMed ID | 26002462 | Mgi Jnum | J:221102 |
| Mgi Id | MGI:5638119 | Doi | 10.1016/j.bbrc.2015.05.050 |
| Citation | Kim TY, et al. (2015) Absence-like seizures and their pharmacological profile in tottering-6j mice. Biochem Biophys Res Commun 463(1-2):148-53 |
| abstractText | 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 alpha1 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 alpha1 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. |
