Inhibition of NMDA-induced outward currents by interleukin-1beta in hippocampal neurons.
There is increasing evidence that a functional interaction exists between interleukin-1beta (IL-1beta) and N-methyl-D-aspartate (NMDA) receptors. The present study attempted to elucidate the effect of IL-1beta on the NMDA-induced outward currents in mechanically dissociated hippocampal neurons using a perforated patch recording technique. IL-1beta (30-100 ng/ml) inhibited the mean amplitude of the NMDA-induced outward currents that were mediated by charybdotoxin (ChTX)-sensitive Ca(2+)-activated K(+) (K(Ca)) channels. IL-1beta (100 ng/ml) also significantly increased the mean ratio of the NMDA-induced inward current amplitudes measured at the end to the beginning of a 20-s application of NMDA. In hippocampal neurons from acute slice preparations, IL-1beta significantly inhibited ChTX-sensitive K(Ca) currents induced by a depolarizing voltage-step. IL-1 receptor antagonist antagonized effects of IL-1beta. These results strongly suggest that IL-1beta increases the neuronal excitability by inhibition of ChTX-sensitive K(Ca) channels activated by Ca(2+) influx through both NMDA receptors and voltage-gated Ca(2+) channels.
Laboratory of Oral Aging Science, Faculty of Dental Sciences, Kyushu University, Maidashi 3-1-1, Fukuoka 812-8582, Japan.
Ruoyu
R
Zhang
Jun
J
Yamada
Yoshinori
Y
Hayashi
Zhou
Z
Wu
Susumu
S
Koyama
Hiroshi
H
Nakanishi
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002469:Cell Separation; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D053583:Interleukin-1beta / Q000494:pharmacology / Q000502:physiology*; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*
D053583:Interleukin-1beta; D015221:Potassium Channels; D016194:Receptors, N-Methyl-D-Aspartate; C087375:charybdotoxin receptor; D016202:N-Methylaspartate; D002118:Calcium