多巴胺对大鼠前额叶皮层锥体神经元NMDA受体通道的影响

Influence of Dopamine on NMDA Receptor Channel of Pyramidal Neurons in Prefrontal Cortex in Rat

【目的】探讨多巴胺(DA)对前额叶皮层锥体神经元谷氨酸/N-甲基-D-天冬氨酸(NMDA)受体的调节作用。【方法】使用细胞贴附式膜片钳技术进行单通道记录,观察不同浓度DA对急性分离的前额叶皮层锥体神经元NMDA受体通道电流的影响。【结果】结果表明:当DA浓度为0逐渐升高到60!mol/L时,NMDA受体通道的电流幅度由(2.78+0.68)pA升高到(5.42+1.26)pA;短开放时间常数变化不明显,但长开放时间常数由(13.59+1.26)ms升高到(36.19+1.17)ms;长关闭时间常数由(19.73+1.46)ms降低到(2.67+0.75)ms;通道开放概率由0.25+0.09升高到0.56+0.25;当DA浓度继续由60!mol/L升高到100!mol/L时,NMDA受体通道的电流幅度回落到(3.56+0.79)pA,长开放时间常数回落到(14.40+1.37)ms;长关闭时间常数恢复为(17.74+1.79)ms,与对照组比较无显著性变化;通道开放概率由0.56+0.25降低到0.17+0.08。【结论】DA可以影响前额叶皮层锥体神经元NMDA受体通道的活动,而且具有浓度依赖性,低浓度有明显促进作用,高浓度则促进作用减弱,甚至有抑制作用。

[ Objective ] To investigate the modulatory effects of dopamine （DA） on N-methyl-D-aspartate （NMDA） receptor channels of the pyramidal neurons in prefrontal cortex in rat. [ Methods ] Cell-attached configuration of patch clamp was used to record single-channel currents of NMDA receptors. The effect of DA in different concentration on the electricity of NMDA receptor channel was observed.[Results] When the concentrations of DA increased gradually from 0 to 60 μmol/L, the amplitude of NMDA receptor channel currents was increased from （2.78±0.68） pA to （5.42±1.26） pA; the short open-time-constant did not change significantly, the long open-time- constant increased from （13.59±1.26） ms to （36.19±1.17） ms, and open probability of inward currents of NMDA receptor channels increased from 0.25±0.09 to 0.56±0.25; and the long closing-time-constant decreased from （9.73±1.46） ms to （2.67±0.75） ms. However, when the concentrations of DA increased from 60 μmol/L to 100 umol/L, the amplitude of NMDA receptor channel currents was decreased to （3.56±0.79） pA, long open-time-constant decreased to （14.40±1.37） ms, long closing-time-constant restored to （17.74±1.79） ms, and the open probability of NMDA receptor-channel decreased to 0.17±0.08. [Conclusion] DA could affect the activities of NMDA receptor channels, but there was relationship of reverted U shape and the increases in concentrations of dopamine. At low concentrations, DA enhanced the activation of NMDA receptor channels, but inhibited the activation of NMDA receptor chan- nels at high concentrations.