title: Upregulated expression of voltage-gated sodium channel Nav1.3 in cortical lesions of patients with focal cortical dysplasia type IIb.
abstract: Focal cortical dysplasia (FCD) is one of the causes of intractable epilepsy in humans. Cytomegalic neurons, not balloon cells, are considered to be the putative generators of epileptic activity in FCD type IIb (FCDIIb). Voltage-gated sodium channel III α-isoforms (Nav1.3) play crucial roles in the initiation and propagation of action potentials and are important regulators of neuronal excitability. Here, we examined 12 FCDIIb surgical specimens from patients undergoing surgery for epilepsy and used age-matched normal control cortical tissue (CTX) from 10 autopsy samples as controls. Using reverse transcription-PCR and western blot techniques, we found that the mRNA and protein levels of Nav1.3 were clearly upregulated in FCDIIb surgical specimens compared with the controls (CTX). Results of immunohistochemistry analyses demonstrated that Nav1.3 immunoreactivity was widely present in FCDIIb lesion tissue; specifically, high levels of Nav1.3 immunoreactive proteins were located mainly in cytomegalic neurons of different sizes and shapes, not in balloon cells. Double-labeling studies showed most cytomegalic neurons expressing Nav1.3 colabeled with neuronal markers and glutamate receptors-1. Taken together, our results show an upregulation of Nav1.3 protein and a specific cellular distribution of Nav1.3 proteins in FCDIIb lesion tissue samples, suggesting that Nav1.3 may be involved in the generation of epileptic activity in FCDIIb.
authors.affiliation: Department of Neurosurgery, Xinqiao Hospital, Chongqing, People's Republic of China.
authors.forename: Sixun
authors.initials: S
authors.lastname: Yu
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.forename: Haifeng
authors.initials: H
authors.lastname: Shu
authors.forename: Chunqing
authors.initials: C
authors.lastname: Zhang
authors.forename: Jiaojiang
authors.initials: J
authors.lastname: He
authors.forename: Xiaotang
authors.initials: X
authors.lastname: Fan
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
mesh_terms: D002540:Cerebral Cortex / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000209:etiology / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D054220:Malformations of Cortical Development / Q000150:complications / Q000473:pathology*; D062552:NAV1.3 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D062552:NAV1.3 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C424715:SCN3A protein, human; D015222:Sodium Channels