Ca(v)3.1 T-type calcium channel modulates the epileptogenicity of hippocampal seizures in the kainic acid-induced temporal lobe epilepsy model

Abstract

The molecular mechanism of temporal lobe epilepsy has not been clearly identified. T-type calcium channels play a role in burst firing in neurons and have been implicated in several seizure models. In this study, the role of Ca(v)3.1 T-type (alpha 1G) calcium channel has been investigated in the kainic acid (KA)-induced temporal lobe epilepsy model (TLE) by using conventional alpha 1G knock-out (ko) mice. After intraperitoneal (i.p.) administration or intrahippocampal injection of KA, depth hippocampal and cortical electroencephalogram (EEG) and behavioral monitoring were recorded, and timm and Nissl staining of brain sections were made later. Seizure was mainly identified by EEG signals, rather than behaviorally, with analytic criteria. During the acute status epilepticus (SE) period, both the duration and the frequency of hippocampal seizures were significantly reduced and increased, respectively, in alpha lG ko mice compared to those of wild type mice. Epileptogenicity, the total period of seizures (hr(-1)), was also significantly reduced in alpha 1G ko mice. However, the latency of seizure occurrence was not significantly different between wild type and ko mice. These differential effects were not observed in cortical seizures. Furthermore, the injection of KA caused a strong increase in 3 rhythm power spectrum density (PSD) of EEG in alpha lG ko mice compared to that in wild type mice. The results with conventional ko mice indicate that alpha 1G T-type calcium channel plays a modulatory role in the duration and frequency of hippocampal seizures as well as the epileptogenicity of KA-induced TLE in mice, mostly during acute periods. (C) 2015 Elsevier B.V. All rights reserved.