利多卡因对大鼠海马锥体神经元GABA_A-Cl^-电流的影响

Effect of Lidocaine on GABA_A-Cl^- Current of Hippocampal Pyramidal Neurons of Rats

目的 研究利多卡因对大鼠海马锥体神经元全细胞γ 氨基丁酸介导的氯电流 (GABA Cl-电流 )的影响 ,及其中枢致惊厥作用的可能机制。方法 酶解急性分离 2周龄左右大鼠海马锥体神经元 ,采用全细胞膜片钳技术 ,记录利多卡因对单个海马锥体神经元GABA Cl-电流的影响。结果 将钳制电位固定在 - 6 0mV ,GA BA以剂量依赖性方式诱导出内向电流 ;利多卡因明显抑制GABA诱导的Cl-电流 (IGABA) ,5 0 %抑制浓度 (IC50 )为 4 .0 5mmol/L ,10mmol/L可使GABA浓度效应曲线明显右移 ,5 0 %有效浓度 (EC50 )由 7.72mmol/L增加到17.2mmol/L ,且最大电流明显降低。结论 利多卡因以非竞争性的方式 ,抑制海马锥体神经元GABAA Cl-电流 ,可能是其中枢致惊厥作用的机制。

Purpose To evaluate the effect of lidocaine on the gamma-aminobutyric acid mediated Cl- current (GABA A?Cl- current, I GABA) of acutely dissociated hippocampal pyramidal neurons of rat and to reveal the probable mechanism of inducing seizure by lidocaine. Methods Patch-clamp technique was applied to freshly dissociated hippocampal pyramidal neurons of 2-3 weeks old rats.Under voltage-clamp conditions,the whole-cell I GABA were recorded in the presence of different concentration of lidocaine. Results In the pyramidal neurons voltage-clamped at -60 mV,GABA evoked a transmembrane inward current and the peak amplitude of the current increased sigmoidally with increasing doses of GABA applied. Co-application of lidocaine resulted in a decline of IGABA and the IC 50 was 4.05 mmol/L.10 mmol/L lidocaine resulted in right shift of concentration-response curve and not only EC 50 changing from 7.72 mmol/L to 17.2 mmol/L but also the maximal current unable to reach the top level. Conclusions Lidocaine inhibited the I GABA of hippocampial pyramidal neurons by non-competitive manner.The suppression of I GABA may contribute to lidocaine-induced seizures.