Effects of interleukin-1β on hippocampal glutamate and GABA releases associated with Ca2+-induced Ca2+ releasing systems

Recent clinical and basic studies have demonstrated that hyperactivation of interleukin-1β (IL-1β) plays important roles in generation of febrile and epileptic seizures. To clarify this mechanism, the present study determined the effects of IL-1β on Ca2+-associated releases of glutamate and GABA in mouse hippocampus. Both basal and K+-evoked GABA releases were regulated by Ca2+ influx and Ca2+-induced Ca2+ releasing system (CICR). The K+-evoked glutamate release was also regulated by Ca2+ influx and CICR, whereas basal glutamate release was not affected by them. IL-1β increased basal releases of glutamate and GABA depending on the activation of Ca2+ influx and ryanodine receptor (RyR)-sensitive CICR, but reduced K+-evoked releases depending on Ca2+ influx, RyR-sensitive and inositol 1,4,5-trisphosphate receptor (IP3R)-sensitive CICRs. During neuronal hyperexcitability, the effect of IL-1β on GABA release was more predominantly modulated by Ca2+ influx and RyR-sensitive CICR than that on glutamate. These results indicate that hyperactivation of IL-1β leads to imbalance between glutamatergic and GABAergic transmission via toxic overload response of Ca2+ influx and CICR.