There is increasing evidence that a functional interaction exists between interleukin-1 beta (IL-1 beta) and N-methyl-D-aspartate (NMDA) receptors. The present study attempted to elucidate the effect of IL-1 beta on the NMDA-induced outward currents in mechanically dissociated hippocampal neurons using a perforated patch recording technique. IL-1 beta (30-100 ng/ml) inhibited the mean amplitude of the NMDA-induced outward currents that were mediated by charybdotoxin (ChTX)-sensitive Ca2+-activated K+ (K-Ca) channels. IL-1 beta (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-1 beta significantly inhibited ChTX-sensitive K-Ca currents induced by a depolarizing voltage-step. IL-1 receptor antagonist antagonized effects of IL-1 beta. These results strongly suggest that IL-1 beta increases the neuronal excitability by inhibition of ChTX-sensitive K-Ca channels activated by Ca2+ influx through both NMDA receptors and voltage-gated Ca2+ channels. (c) 2008 Elsevier Inc. All rights reserved.