Protein kinase C-ε contributes to a chronic inhibitory effect of IL-1β on voltage-gated sodium channels in mice with febrile seizure.

This study aimed to understand the role of Interleukin-1 beta in mouse febrile seizures. To investigate the chronic effects of raised Interleukin-1 beta on seizures, the sodium currents of hippocampal neurons were recorded by whole-cell voltage clamp. Interleukin-1 beta inhibited sodium currents in mouse hippocampal neurons and verified that protein kinase C epsilon contributed to the effect of Interleukin-1 beta 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-1 beta treatment, and was abolished following the administration of a protein kinase C epsilon inhibitor, epsilon V1-2. However, neither Interleukin-1 beta nor epsilon V1-2 had any significant effect on spike threshold. Interleukin-1 beta 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 neuro-excitability, 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-1 beta on hippocampal neurons.