Open AccessProtein kinase C-ε contributes to a chronic inhibitory effect of IL-1β on voltage-gated sodium channels in mice with febrile seizure
Author(s) -
Jinli Wang,
Fengming Xu,
Yi Zheng,
Chunfang Xu,
Piaopiao Zhang,
Hongyang Zhao
Publication year - 2019
Publication title -
journal of integrative neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.336
H-Index - 33
eISSN - 1757-448X
pISSN - 0219-6352
DOI - 10.31083/j.jin.2019.02.145
Subject(s) - sodium channel , neuroprotection , hippocampal formation , protein kinase a , depolarization , pharmacology , inhibitory postsynaptic potential , patch clamp , status epilepticus , chemistry , endocrinology , medicine , kinase , biology , neuroscience , electrophysiology , epilepsy , sodium , biochemistry , organic chemistry
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 εV1-2 had any significant effect on spike threshold. Interleukin-1β 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.