Developmental change of the inhibition by lead of NMDA-activated currents in cultured hippocampal neurons.
Developmental change of the inhibition by lead of NMDA-activated currents in cultured hippocampal neurons.
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发表时间：
1992-11
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通讯作者：
H. Ujihara;E. Albuquerque
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作者：
H. Ujihara;E. Albuquerque
在细胞发育的各个阶段研究了 Pb2+ 对培养的胎鼠海马神经元中 N-甲基-D-天冬氨酸 (NMDA) 激活电流的抑制作用。 Pb2+ 选择性抑制年轻培养神经元记录的 NMDA 电流。在培养的第一周，Pb2+表现出最显着的抑制作用，在接下来的几周内逐渐减弱。 Pb2+ 的作用对 NMDA- 具有选择性，而不是红藻氨酸或使君子酸盐诱导的电流。 Pb2+ 存在下 NMDA 感应电流的电流-电压关系表明，该阳离子的作用与电压无关，这表明 Pb2+ 与 NMDA 受体/通道相互作用的位点位于膜电场之外。单通道研究表明，Pb2+ 会降低 NMDA 激活的单通道电流的频率，但不会降低其寿命。进一步评估 Pb2+ 对 NMDA 受体的作用机制表明，该阳离子是 NMDA 和甘氨酸的非竞争性拮抗剂。我们已经证明，NMDA 诱导的全细胞电流随着细胞发育而变化，并且 Pb2+ 的影响也取决于培养年龄。在培养的大鼠海马神经元中，NMDA 诱导的电流有两种成分，一种快速衰减，另一种缓慢衰减。在甘氨酸浓度高于 1 µM 时可以清楚地观察到快成分，而慢成分在甘氨酸浓度为 1 µM 时达到其最大振幅。此外，NMDA诱发的全细胞电流的快速衰减成分在年轻的培养神经元中占主导地位，而其对总电流的贡献在年老的培养神经元中减少。（摘要截断为250字）
The inhibition of N-methyl-D-aspartate (NMDA)-activated current in cultured fetal rat hippocampal neurons by Pb2+ was investigated at various stages of cell development. Pb2+ selectively inhibited NMDA currents recorded from young cultured neurons. In the first week of culture, Pb2+ showed the most prominent inhibition, which was gradually attenuated in the following weeks. Pb2+'s action was selective for NMDA- as opposed to either kainate- or quisqualate-induced currents. The current-voltage relationship for NMDA-induced currents in the presence of Pb2+ revealed that the effect of this cation was voltage-independent, which suggested that the site of interaction of Pb2+ with the NMDA receptor/channel is located outside the membrane electric field. Single channel studies showed that Pb2+ reduced the frequency but not the lifetime of the NMDA-activated single channel currents. Further evaluation of the mechanism of action of Pb2+ on the NMDA receptor demonstrated that this cation is a noncompetitive antagonist of both NMDA and glycine. We have demonstrated that the NMDA-induced whole cell currents change along with cell development, and the effects of Pb2+ are also dependent upon age of culture. The NMDA-induced currents in cultured rat hippocampal neurons had two components, one that decayed rapidly and another that decayed slowly. The fast component was clearly observed at concentrations of glycine higher than 1 microM, whereas the slow component reached its maximum amplitude at the glycine concentration of 1 microM. Moreover, the rapidly decaying component of NMDA-evoked whole cell currents was predominant in young cultured neurons, and its contribution to the total current was reduced in old cultured neurons.(ABSTRACT TRUNCATED AT 250 WORDS)