Effects of interleukin-1beta on hippocampal glutamate and GABA releases associated with Ca2+-induced Ca2+ releasing systems.
Recent clinical and basic studies have demonstrated that hyperactivation of interleukin-1beta (IL-1beta) plays important roles in generation of febrile and epileptic seizures. To clarify this mechanism, the present study determined the effects of IL-1beta 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-1beta 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-1beta 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-1beta leads to imbalance between glutamatergic and GABAergic transmission via toxic overload response of Ca2+ influx and CICR.
Zhu
Gang
G
Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki 036-8562, Japan.
Okada
Motohiro
M
Yoshida
Shukuko
S
Mori
Fumiaki
F
Ueno
Shinya
S
Wakabayashi
Koichi
K
Kaneko
Sunao
S
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects*; D002555:Cerebrospinal Fluid; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000096:biosynthesis*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis*
D015220:Calcium Channels; D003470:Culture Media; D007375:Interleukin-1; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D002118:Calcium