氯胺酮对大鼠海马神经元瞬间外向钾电流的抑制作用

Suppression effect of ketamine on transient outward potassium currents in rathippocampal neurons

目的:观察氯胺酮对大鼠海马锥体神经元瞬间外向钾电流(IA)的影响。方法:酶消化法急性分离Wistar大鼠海马锥体神经元,采用全细胞膜片钳技术测定IA。加用不同浓度(10、30、100、300和1 000μmol/L)氯胺酮后,计算IA抑制率,建立氯胺酮的浓度-效应曲线,选择30μmol/L氯胺酮作IA稳态激活(及失活)曲线。结果:10μmol/L的氯胺酮对IA的电流幅度无影响;30、100、300和1 000μmol/L的氯胺酮对IA的电流幅度抑制率分别为(11±2)%、(22±3)%、(45±5)%和(53±5)%。IC50为(130±24)μmol/L,Hill系数为1.19±0.56。30μmol/L氯胺酮使激活曲线的半数最大激活膜电位(V1/2)从(-8.70±0.13)mV移动到(-11.2±2.10)mV(n=8,P<0.05),K从(15.0±4.6)mV移动到(17.6±5.7)mV(n=8,P>0.05);失活曲线的V1/2从(-75.53±7.98)mV移动到(-91.94±11.85)mV(n=8,P<0.05),K从(10.5±2.2)mV移动到(8.0±1.2)mV(n=8,P>0.05)。30μmol/L氯胺酮使IA的激活和失活曲线均向超极化方向明显移动。结论:临床浓度的氯胺酮能够同时加速IA的激活和失活过程,但加速IA失活的能力大于其加速IA激活的能力。氯胺酮对中枢神经系统的作用可能与IA抑制有关。

Objective：To investigate the effect of ketamine on the transient outward potassium currents（IA） using whole-cell patch clamp technique.Methods： Pyramidal neurons were enzymatically isolated from Wistar rat hippocampus.The effect of ketamine on the IA was assessed using whole-cell patch clamp technique.Different concentrations of ketamine were added and potassium currents were measured.Results： IA was inhibited by ketamine in a concentration-dependent manner.10 μmol/L ketamine had no effect on IA.The four concentrations of ketamine（30,100,300,1 000 μmol/L） reduced peak IA currents by（11±2）%,（22±3）%,（45±5）%,（53±5）% respectively,with a mean IC50 of（130±24） μmol/L and Hill coefficient of 1.19±0.56.The V1/ 2 of activation curve was shifted from（-8.70±0.13） mV to（-11.2±2.10） mV（n=8,P〈0.05）.The V1/ 2 of inactivation curve was shifted from（-75.53±7.98） mV to（-91.94±11.85） mV（n=8,P〈0.05）.Conclusion： Ke-tamine produces significant inhibition of potassium currents in the central neurons,which may least partly explain at the action of ketamine.