title: Abnormal changes in voltage-gated sodium channels Na(V)1.1, Na(V)1.2, Na(V)1.3, Na(V)1.6 and in calmodulin/calmodulin-dependent protein kinase II, within the brains of spontaneously epileptic rats and tremor rats.
abstract: Voltage-gated sodium channels (VGSCs) play a crucial role in epilepsy. The expressions of different VGSCs subtypes are varied in diverse animal models of epilepsy that may reflect their multiple phenotypes or the complexity of the mechanisms of epilepsy. In a previous study, we reported that NaV1.1 and NaV1.3 were up-regulated in the hippocampus of the spontaneously epileptic rat (SER). In this study, we further analyzed both the expression and distribution of the typical VGSC subtypes NaV1.1, NaV1.2, NaV1.3 and NaV1.6 in the hippocampus and in the cortex of the temporal lobe of two genetic epileptic animal models: the SER and the tremor rat (TRM). The expressions of calmodulin (CaM) and calmodulin-dependent protein kinase II (CaMKII) were also analyzed with the purpose of assessing the effect of the CaM/CaMKII pathway in these two models of epilepsy. Increased expression of the four VGSC subtypes and CaM, accompanied by a decrease in CaMKII was observed in the hippocampus of both the SERs and the TRM rats. However, the changes observed in the expression of VGSC subtypes and CaM were decreased with an elevated CaMKII in the cortex of their temporal lobes. Double-labeled immunofluorescence data suggested that in SERs and TRM rats, the four subtypes of the VGSC proteins were present throughout the CA1, CA3 and dentate gyrus regions of the hippocampus and temporal lobe cortex and these were co-localized in neurons with CaM. These data represent the first evidence of abnormal changes in expression of four VGSC subtypes (NaV1.1, NaV1.2, NaV1.3 and NaV1.6) and CaM/CaMKII in the hippocampus and temporal lobe cortex of SERs and TRM rats. These changes may be involved in the generation of epileptiform activity and underlie the observed seizure phenotype in these rat models of genetic epilepsy.
authors.affiliation: Biochip Center, Department of Basic Medicine, China Medical University, Shenyang 110001, China.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Xu
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.forename: Xintong
authors.initials: X
authors.lastname: Lv
authors.forename: Rui
authors.initials: R
authors.lastname: Feng
authors.forename: Dongyu
authors.initials: D
authors.lastname: Min
authors.forename: Lihua
authors.initials: L
authors.lastname: Ma
authors.forename: Yajing
authors.initials: Y
authors.lastname: Liu
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Zhao
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Tianbao
authors.initials: T
authors.lastname: Chen
authors.forename: Chris
authors.initials: C
authors.lastname: Shaw
authors.forename: Liying
authors.initials: L
authors.lastname: Hao
authors.forename: Jiqun
authors.initials: J
authors.lastname: Cai
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000378:metabolism*; D005260:Female; D015640:Ion Channel Gating / Q000502:physiology; D008297:Male; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D014202:Tremor / Q000378:metabolism*
chemical_list: D002147:Calmodulin; D015222:Sodium Channels; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: Calmodulin; Calmodulin-dependent protein kinase II; Genetic epilepsy; Subtype; Voltage-gated sodium channel