title: The up-regulation of voltage-gated sodium channels subtypes coincides with an increased sodium current in hippocampal neuronal culture model.
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 (I(Na,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 (I(Na,P)) was obviously increased in the hippocampal neuronal culture model as judged by single-channel patch-clamp recording. Furthermore, VGSC subtypes Na(V)1.1, Na(V)1.2 and Na(V)1.3 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.
authors: Department of Pharmaceutical Toxicology, School of Pharmaceutical Science, China Medical University, Shenyang 110001, China.
authors: Feng
authors: F
authors: Guo
authors: Xiaoxue
authors: X
authors: Xu
authors: Jiqun
authors: J
authors: Cai
authors: Huiyuan
authors: H
authors: Hu
authors: Wei
authors: W
authors: Sun
authors: Guilin
authors: G
authors: He
authors: Dongxue
authors: D
authors: Shao
authors: Lei
authors: L
authors: Wang
authors: Tianbao
authors: T
authors: Chen
authors: Chris
authors: C
authors: Shaw
authors: Tong
authors: T
authors: Zhu
authors: Liying
authors: L
authors: Hao
mesh_terms: D000818:Animals; D004827:Epilepsy / Q000503:physiopathology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D015640:Ion Channel Gating; D008954:Models, Biological; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D015222:Sodium Channels