硫喷妥钠对N-甲基-D-天冬氨酸门控电流的影响。

Effect of thiopental sodium on N-methyl-D-aspartate-gated currents.

作者信息

Liu Hongliang, Dai Tijun, Yao Shanglong

机构信息

Department of Anesthesiology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu province, 210000, China.

出版信息

Can J Anaesth. 2006 May;53(5):442-8. doi: 10.1007/BF03022615.

DOI:10.1007/BF03022615

PMID:16636027

Abstract

PURPOSE

N-methyl-D-aspartate (NMDA) receptors in the prefrontal cortex (PFC) are closely related with the excitability of pyramidal neurons and PFC function. As the effect of thiopental sodium on the central nervous system may partly result from the inhibition of PFC NMDA receptors, we investigated the effect of thiopental sodium with different concentrations on NMDA-gated currents in acutely dissociated rat PFC pyramidal neurons. We sought to determine whether thiopental sodium inhibits NMDA receptor function.

METHODS

Three to four week old male Sprague-Dawley rats were sacrificed and the PFC was dissected. Pyramidal neurons from the PFC were prepared and standard whole-cell patch clamp recordings were performed. Escalating concentrations from 3-1000 microM NMDA were applied 100 microm from the pyramidal cells, and the concentration in the effect compartment related to 50% effect (EC50) of NMDA was determined for the ensuing experiments. One hundred microM NMDA alone (control) or NMDA with different concentrations (10-1000 microM) of thiopental sodium were applied. After the inhibitory concentration, in 50% of NMDA effect (IC50) of thiopental sodium was established this IC50 and NMDA 3-1000 microM were applied 100 microm from the pyramidal cells. The EC50 value of NMDA under the effect of IC50 thiopental sodium was determined.

RESULTS

N-methyl-D-aspartate induced inward currents in a concentration-dependent manner, which were completely antagonized by 50 microM AP5. The maximal amplitude of NMDA-induced current was 1.15 +/- 0.27 nA. The EC50 of NMDA was 53.6 +/- 12.4 microM. The NMDA (100 microM)-gated current was inhibited by thiopental sodium in a concentration-dependent manner, and the IC50 of thiopental sodium was 33.6 +/- 6.1 microM. Under the effect of 33.6 microM thiopental sodium, the maximal amplitude of NMDA-induced current was 0.87 +/- 0.17 nA. The concentration-response curve of NMDA was shifted rightwards. The EC50 of NMDA was 128 +/- 15 microM, which was greater than that of NMDA without thiopental sodium (P < 0.01).

CONCLUSIONS

Thiopental sodium decreases NMDA-gated currents in acutely dissociated rat prefrontal cortical pyramidal neurons in a concentration-dependent manner.

摘要

目的

前额叶皮质（PFC）中的N-甲基-D-天冬氨酸（NMDA）受体与锥体神经元的兴奋性及PFC功能密切相关。由于硫喷妥钠对中枢神经系统的作用可能部分源于对PFC中NMDA受体的抑制，我们研究了不同浓度硫喷妥钠对急性分离的大鼠PFC锥体神经元中NMDA门控电流的影响。我们试图确定硫喷妥钠是否抑制NMDA受体功能。

方法

处死3至4周龄的雄性Sprague-Dawley大鼠并解剖出PFC。制备PFC中的锥体神经元并进行标准的全细胞膜片钳记录。从距离锥体细胞100微米处施加浓度从3至1000微摩尔/升递增的NMDA，随后的实验中测定与NMDA 50%效应（EC50）相关的效应室浓度。单独施加100微摩尔/升NMDA（对照）或与不同浓度（10至1000微摩尔/升）硫喷妥钠一起施加NMDA。确定硫喷妥钠在NMDA 50%效应时的抑制浓度（IC50）后，从距离锥体细胞100微米处施加该IC50和3至1000微摩尔/升NMDA。测定在IC50硫喷妥钠作用下NMDA的EC50值。

结果

NMDA以浓度依赖性方式诱导内向电流，50微摩尔/升的AP5可完全拮抗该电流。NMDA诱导电流的最大幅度为1.15±0.27纳安。NMDA的EC50为53.6±12.4微摩尔/升。硫喷妥钠以浓度依赖性方式抑制NMDA（100微摩尔/升）门控电流，硫喷妥钠的IC50为33.6±6.1微摩尔/升。在33.6微摩尔/升硫喷妥钠作用下，NMDA诱导电流的最大幅度为0.87±0.17纳安。NMDA的浓度-反应曲线向右移动。NMDA的EC50为128±15微摩尔/升，大于无硫喷妥钠时NMDA的EC50（P<0.01）。