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Journal of Integrative Neuroscience  2019, Vol. 18 Issue (2): 173-179    DOI: 10.31083/j.jin.2019.02.145
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Protein kinase C-ε contributes to a chronic inhibitory effect of IL-1β on voltage-gated sodium channels in mice with febrile seizure
Jinli Wang1, Fenfen Xu1, Yuan Zheng1, Xu Cheng2, Piaopiao Zhang2, Hongyang Zhao1, *()
1 Department of Pediatrics, Jinan Central Hospital Affiliated to Shandong University, Jinan City, Shandong Province, 250013, P. R. China
2 Graduate School of Taishan Medical University, Taian City, Shandong Province, 271016, P. R. China
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Abstract  

This study aimed to understand the role of Interleukin-1β in mouse febrile seizures. To investigate the chronic effects of raised Interleukin-1β on seizures, the sodium currents of hippocampal neurons were recorded by whole-cell voltage clamp. Interleukin-1β inhibited sodium currents in mouse hippocampal neurons and verified that protein kinase C epsilon contributed to the effect of Interleukin-1β exposure. The inhibitory effect was also identified in neurons from a protein kinase C epsilon null mutant mouse. Action potentials were recorded using a ramp depolarizing current. Peak spike depolarization was significantly reduced by Interleukin-1β treatment, and was abolished following the administration of a protein kinase C epsilon inhibitor, εV1-2. However, neither Interleukin-1β nor εV12 had any significant effect on spike thrβ reduced the amplitude of action potentials due to its inhibitory effect on sodium channels. This is hypothesised to decrease the release of presynaptic transmitters of neuroexcitability, thus exerting a neuroprotective role in excitotoxicity. To ascertain the role of protein kinase C epsilon on febrile seizures in vivo, a heated water-bath model was used to identify susceptible mice. It was found that protein kinase C epsilon reduced susceptibility to, and frequency of, febrile seizure onset. This may be related to the neuroprotective effect of Interleukin-1β on hippocampal neurons.

Key words:  Febrile seizure      IL-1β      hippocampus      voltage-gated sodium channel      PKC-ε     
Submitted:  26 March 2019      Accepted:  26 June 2019      Published:  30 June 2019     
*Corresponding Author(s):  Hongyang Zhao     E-mail:  zhy1587@zxyy.cn

Cite this article: 

Jinli Wang, Fenfen Xu, Yuan Zheng, Xu Cheng, Piaopiao Zhang, Hongyang Zhao. Protein kinase C-ε contributes to a chronic inhibitory effect of IL-1β on voltage-gated sodium channels in mice with febrile seizure. Journal of Integrative Neuroscience, 2019, 18(2): 173-179.

URL: 

https://jin.imrpress.com/EN/10.31083/j.jin.2019.02.145     OR     https://jin.imrpress.com/EN/Y2019/V18/I2/173

Figure 1.  The inhibitory effect of IL-1β on Na+ currents was dependent on PKC-ε in mouse hippocampal neurons. A, whole-cell current recording of the Na+ currents in mouse hippocampal neurons (n = 10). Neurons cultured without IL-1β treatment (Left) and with 10 ng/ml of IL-1β (Right) for 12 hours. B, Comparison of current density-voltage curves between no treatment and 10 ng/ml (12 h) of IL-1β (P < 0.05; n = 10; Student's t-test), as compared with no IL-1β (*P < 0.05). C, Time course of the inhibitory effects of IL-1β on Na+ current (n = 10). Data normalized to current magnitude prior to IL-1β treatment. D, Inhibitory effect of IL-1β abolished by εV1-2, an inhibitor of PKC-ε (n = 10), as compared with the no IL-1β group (**P < 0.01); as compared with IL-1β group (##P < 0.01, Student's t-test).

Figure 2.  The inhibitory effect of IL-1β on Na+ currents was dependent on PKC-ε in vivo. 10 ng/ml of IL-1β was added in the culture of the hippocampal neurons isolated from PKC-ε-/- mice (n = 10) and wild-type littermates PKC-ε+/+ (n = 10). Data were normalized to the current of neurons from PKC-ε+/+ mice not treated with IL-1β. The mean minimal current of ε+/+ mice was inhibited by 56.1 ± 5.1%, which was significantly different from PKC-ε-/- mice (P < 0.05), as compared with 10 ng/ml of IL-1β, PKC-ε-/- group (*P < 0.05 and **P < 0.01).

Figure 3.  Effect of IL-1β and PKC-ε inhibitor εV1-2 on spike amplitude and threshold examined by current-clamp recording (n = 10). as compared with no IL-1β group (**P < 0.01); as compared with IL1β group (##P < 0.01, Student's t-test).

Figure 4.  The susceptibility and frequency of mice (n = 10) with FS after injection of εV1-2. (A) PKC-ε inhibitor significantly reduced seizure frequency (P < 0.01) and (C) duration (P < 0.01), (B) but had no significant impact on response latency (P > 0.05), as compared with the t-test). tured in 10 ng/ml of IL-1β for 12 FS group (*P < 0.05 and **P < 0.01).

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