Araneda R C, Zukin R S, Bennett M V
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461.
Neurosci Lett. 1993 Apr 2;152(1-2):107-12. doi: 10.1016/0304-3940(93)90495-7.
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.
在来自胚胎大鼠的培养海马神经元中，研究了多胺精胺和亚精胺对NMDA诱导电流的作用。在使用电压钳的全细胞膜片实验中，精胺（300微摩尔）使对NMDA的反应（在-70毫伏且存在饱和甘氨酸的情况下）增强了约两倍；在207微摩尔时产生半数最大增强效应。精胺在正电位时产生的增强作用稍大。增强作用的起始很快（t1/2 < 1秒），表明作用位点在细胞外。亚精胺在增强NMDA反应方面效力相当，但不如精胺有效。在切除的外侧向外膜片中，精胺对NMDA诱导的单通道反应表现出两种作用。在一些膜片中，它增加了通道开放概率；通道开放频率和爆发长度均增加，而平均开放持续时间无显著变化，这在很大程度上解释了全细胞实验中观察到的增强作用。在所有膜片中，精胺在负电压下降低通道电导，这种效应可归因于快速通道阻断（可能有电荷筛选的作用）。这些结果与多胺在NMDA受体不同位点介导的相反作用一致。
