氯胺酮对大鼠颈上交感神经节神经元烟碱诱发电流的影响

Effect of ketamine on nicotine-induced current in rat superior cervical ganglion neurons

目的评价氯胺酮对大鼠颈上交感神经节神经元烟碱诱发电流的影响。方法采用胰酶消化法急性分离新生Wistar大鼠颈上交感神经节神经元，接种于培养皿，培养5～7d后采用膜片钳全细胞模式测定烟碱诱发电流，记录50μmol／L烟碱和与不同浓度（10、25、50、100μmol／L）氯胺酮混合溶液作用下烟碱诱发的峰电流及受体失敏时间常数，计算其抑制烟碱诱发电流的半数有效浓度。结果10、25、50和100μmol／L氯胺酮呈浓度依赖性地抑制烟碱诱发的峰电流（P〈0．05）。与50μmol／L烟碱诱发电流相比，氯胺酮50、100μmol／L给药后受体快失敏相和慢失敏相时间常数均缩短（P〈0．05）。氯胺酮对烟碱诱发电流的抑制作用符合指数方程，其抑制烟碱诱发电流的半数有效浓度〈20μmol／L。结论氯胺酮可呈浓度依赖性地抑制大鼠颈上交感神经节神经元烟碱诱发电流，提示氯胺酮对交感神经节神经元活动具有抑制作用，可能是其在某些特定情况下降低血压的机制之一。

Objective To investigate the effect of ketamine on nicotlne-induced current in rat superior cervical ganglion neurons. Methods Newborn Wistar rats were used in this study. Neurons were isolated enzymatically from superior cervical ganglia of newborn rats in an aseptic condition and cultured in 90% DMEM/F12,10% horse serum containing penicillin 100 μg/ml for 5-7 d. Nicotine-induced current was measured and recorded using whole-cell patch clamp technique. A mixture of nicotine 50 ttmol/L and different concentrations of ketamine （ 10, 25, 50, 100 μmol/L） was added to the isolated neurons. The effect of ketaminc on nicotine-induced current was evaluated.Results Nicotine-induced peak current was inhibited by ketamine in a concentration-dependent manner. The time constant of fast and slow desensitizing phase of the nicotine acetylcholine receptor was shortened after being exposed to the mixture of nicotine 50 μmol/L ＋ 50 or 100 μmol/L ketamine as compared to nicotine 50 μmol/L-induced current. The median effective concentration of ketamine inhibiting nicotine-induced current was less than 20 μmol/L. Conclusion Ketamine can decrease nicotine-induced current in rat superior cervical ganglion neurons in a concentration-dependent manner indicating that inhibition of sympathetic activity is involved in the mechanism of decrease in BP by ketamine in specific condition.