The up-regulation of voltage-gated sodium channels subtypes coincides with an increased sodium current in hippocampal neuronal culture model

Feng Guo, Xiaoxue Xu, Jiqun Cai, Huiyuan Hu, Wei Sun, Guilin He, Dongxue Shao, Lei Wang, Tianbao Chen, Chris Shaw, Tong Zhu, Liying Hao

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Voltage-gated sodium channels (VGSC) have been linked to inherited forms of epilepsy. The expression and biophysical properties of VGSC in the hippocampal neuronal culture model have not been clarified. In order to evaluate mechanisms of epileptogenesis that are related to VGSC, we examined the expression and function of VGSC in the hippocampal neuronal culture model in vitro and spontaneously epileptic rats (SER) in vivo. Our data showed that the peak amplitude of transient, rapidly–inactivating Na+ current (INa,T) in model neurons was significantly increased compared with control neurons, and the activation curve was shifted to the negative potentials in model neurons in whole cell recording by patch–clamp. In addition, channel activity of persistent, non-inactivating Na+ current (INa,P) was obviously increased in the hippocampal neuronal culture model as judged by single–channel patch–clamp recording. Furthermore, VGSC subtypes NaV1.1, NaV1.2 and NaV1.3 were up-regulated at the protein expression level in model neurons and SER as assessed by Western blotting. Four subtypes of VGSC proteins in SER were clearly present throughout the hippocampus, including CA1, CA3 and dentate gyrus regions, and neurons expressing VGSC immunoreactivity were also detected in hippocampal neuronal culture model by immunofluorescence. These findings suggested that the up-regulation of voltage-gated sodium channels subtypes in neurons coincided with an increased sodium current in the hippocampal neuronal culture model, providing a possible explanation for the observed seizure discharge and enhanced excitability in epilepsy.
Original languageEnglish
Pages (from-to)287-295
Number of pages9
JournalNeurochemistry International
Volume62
Issue number3
Early online date16 Jan 2013
DOIs
Publication statusPublished - 2013

Keywords

  • Voltage-gated sodium channel; Subtypes; Sodium curret; Epilepsy

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