Kwiecien R, Medina I, Barbin G, Ben-Ari Y
Laboratoire de Neurobiologie et Physiopathologie du Développement, INSERM U29 123, Paris, France.
Eur J Pharmacol. 1993 Nov 16;249(3):325-9. doi: 10.1016/0014-2999(93)90529-q.
The effects of the hypoglycemic sulphonylurea tolbutamide, a marker of K(+)-ATP channels, on the N-methyl-D-aspartate- (NMDA) and kainate-activated currents were studied in rat hippocampal neurons in culture, using the patch-clamp technique in a whole-cell configuration. Tolbutamide (500 microM) reversibly increased the peak amplitude and the steady state level of NMDA- but not kainate-evoked currents. This effect was not glycine dependent as it was observed at low and saturated concentrations of glycine. The affinity of the NMDA receptor-channel complex for glycine did not change in the presence of tolbutamide. The action of tolbutamide on the NMDA-activated current was not mediated by K(+)-ATP channels since CsCl was added intracellularly at concentrations which completely blocked all K+ channels. Possible mechanisms explaining the effect of tolbutamide via the modulation of intracellular messengers are discussed.
使用全细胞膜片钳技术，在培养的大鼠海马神经元中研究了降糖磺脲类药物甲苯磺丁脲（一种K(+)-ATP通道标志物）对N-甲基-D-天冬氨酸（NMDA）和红藻氨酸激活电流的影响。甲苯磺丁脲（500微摩尔）可逆地增加了NMDA诱发电流的峰值幅度和稳态水平，但对红藻氨酸诱发电流没有影响。这种作用不依赖甘氨酸，因为在低浓度和饱和浓度的甘氨酸条件下均观察到该现象。在甲苯磺丁脲存在的情况下，NMDA受体通道复合物对甘氨酸的亲和力没有改变。甲苯磺丁脲对NMDA激活电流的作用不是由K(+)-ATP通道介导的，因为细胞内加入了完全阻断所有K+通道浓度的CsCl。文中讨论了通过调节细胞内信使来解释甲苯磺丁脲作用的可能机制。
