Effects of polyamines on NMDA-induced currents in rat hippocampal neurons: a whole-cell and single-channel study.
Actions of the polyamines spermine and spermidine on NMDA-induced currents were examined in cultured hippocampal neurons from embryonic rat. In whole-cell patch experiments using voltage-clamp, spermine (300 microM) produced about a two-fold potentiation of responses to NMDA (at -70 mV in the presence of saturating glycine); half-maximal potentiation was elicited at 207 microM. The potentiation produced by spermine was somewhat greater at positive potentials. The onset of potentiation was fast (t1/2 < 1 s), indicative of an extracellular site of action. Spermidine was of comparable potency but less efficacious than spermine in potentiating NMDA responses. In excised outside-out patches, spermine exhibited two actions on NMDA-induced single-channel responses. In some patches, it increased the channel open probability; both frequency of channel opening and burst length were increased with no significant change in the mean open duration, which accounted for much of the potentiation seen in whole-cell experiments. In all patches, spermine decreased channel conductance at negative voltages, an effect ascribable to fast channel block (with a possible contribution by charge screening). These results are consistent with opposing actions of polyamines mediated at distinct sites on the NMDA receptor.
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461.
R C
RC
Araneda
R S
RS
Zukin
M V
MV
Bennett
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D002478:Cells, Cultured; D004357:Drug Synergism; D006624:Hippocampus / Q000187:drug effects*; D015640:Ion Channel Gating / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D013095:Spermidine / Q000494:pharmacology*; D013096:Spermine / Q000494:pharmacology*
D013096:Spermine; D016202:N-Methylaspartate; D013095:Spermidine