罗哌卡因对大鼠DRG神经元GABA_A受体激活电流的影响

Effects of ropivacaine on GABA-activated currents in isolated dorsalroot ganglion neurons in rats

目的：研究罗哌卡因对大鼠背根神经节（DRG）神经元γ-氨基丁酸（GABA）介导膜电流的作用,探讨罗哌卡因的镇痛机理。方法：采用全细胞膜片钳技术,观察预灌流罗哌卡因对急性新鲜分离大鼠DRG神经元GABA激活电流（IGABA）的调制作用。结果：①在受检的73个DRG神经元中大多数（65.7%,48/73）对灌流罗哌卡因（0.1~1 000μmol/L）敏感。产生一幅值在0~380 pA具有浓度依赖性的内向电流。②实验中大部分受检细胞（74.5%,73/98）对外加的GABA敏感。浓度为0.1~1 000μmol/LGABA可引起具有剂量依赖性和明显去敏感作用的内向电流,并且这种内向电流能被GABAA受体选择性拮抗剂bicuculline（100μmol/L）所阻断。③预灌流罗哌卡因（0.1~1 000μmol/L）30 s后再灌流GABA能显著增强GABA（100μmol/L）激活电流的幅值。预加罗哌卡因后GABA量效曲线明显上移,EC50为23.46μmol/L;GABA激活电流的最大值较之对照增强约153%。结论：罗哌卡因对DRG神经元GABA激活电流的增强作用,可导致突触前抑制作用增强,这可能是罗哌卡因在硬膜外麻醉中产生镇痛和麻醉作用的原因之一。

Objective： To investigate the effects of ropivavaine on Gamma-aminobutyric acid（GABA）-activated currents in dorsal root ganglion（DRG）neurons in rats and discuss the analgesia mechanism of ropivacaine.Methods： By means of using whole-cell patch-clamp technique,to investigate the modulatory effects of ropivacaine on GABA-activated currents（IGABA）in acutely isolated dorsal root ganglion neurons.Results： ① In 48 out of 73DRG cells（65.7%,48/73）,to perfusion ropivacaine bromide（0.1～1 000 μmol/L） were sensitive.Which produce in 0 to 380 pA current.② The majority of the neurons examined（74.5%,73/98） were sensitive to GABA.Concentration of 1～1 000 μmol/L GABA could activate a concentration-dependent inward current,which manifested obvious desensitization,and the inward currents could be blocked byGABA-receptor selective antagonist of bicuculline（100 μmol/L）.③ After the neurons were treated with ropivacaine（0.1～1000 μmol/L） prior to the application of GABA（100 μmol/L） 30 s,GABA currents were obviously increased.Ropivacaine could make dose-response curve of the GABA up,EC50 is 23.46 μmol/L.Ropivacaine shifted the GABA dose-response curve upward and increased the maximum response to the contrast about 153%.Conclusion： The enhancement of ropivacaine to DRG neurons activation of GABA current,can lead to enhancement of pre-synaptic inhibition at the spinal cord level.This may be one of the reasons for the anesthetic effect and analgesia for ropivacaine in epidural anesthesia.