Mechanisms of halothane action on glycinergic inhibitory synaptic transmission

简介：全身麻醉药对抑制性突触传递的作用是有争议的，既有增强也有抑制。这种模糊性是由于常规实验中间存在兴奋性突触而得到抑制性反应。方法：取新生大鼠脊髓薄片，用含有2 μ M CNQX和10 μ M荷包牡丹碱的林格氏液灌流，并通入95%O2 + 5%CO2。从运动神经元进行全细胞记录（电压钳位在-70mV）。视觉识别附近的中间神经元刺激引起运动神经元的单突触抑制反应。结果：2%氟烷可抑制IPSC（inhibitoryPostSynapticCurrent）并使其恢复。IPSC的振幅为55（±）SY。[)23%（n=15），48（]SY. ±. [)16%（n=8）（平均值（± SD））。[)SD)氟烷作用5 min或10 min后，分别为对照组的1.5%和1.5%。在某些细胞（4/15）中，IPSC在氟烷应用的早期（1- 2 min）略有增加。微灌流甘氨酸可诱发内向电流。2%氟烷可使甘氨酸诱发的电流的幅值和时程增强，洗脱后恢复到对照值。结论：氟烷可增强甘氨酸抑制性传递中的突触后事件。但使用完全相同的制剂，我们报告说，氟烷抑制整体单突触抑制性传输诱发的电刺激突触前。这些结果表明氟烷在甘氨酸能抑制性传递中的主要作用部位是突触前。

Introduction : The action of general anesthetics on the inhibitory synaptic transmission is controversial, both augmentation and suppression are reported. This ambiguity is due to the existence of the excitatory synapse in the middle of the conventional experiment to get the inhibitory response. Now, using the thin slice preparation, monosynaptic inhibitory transmission is available, allowing the measurement of unambiguous action of general anesthetics.Method : Thin slices from the spinal cord of neonatal rats were prepared2, superfused with a Ringer solution containing 2muM CNQX and 10^-muM bicuculline, bubbled with 95% O2 + 5% CO2. Whole cell recordings were made from motoneurons (voltage clamped at -70mV). Nearby interneurons identified visually were stimulated to evoke monosynaptic inhibitory responses in motoneurons. Halothane was dissolved in the superfusing saline through a vaporizer (dial setting 2%) and applied for 10 min.Result : The IPSC (inhibitory Post Synaptic Current) was suppressed by "2%" halothane and recovered. The amplitude of IPSC was 55(]SY.+-。[)23% (n=15), 48(]SY.+-。[)16% (n=8) (mean(]SY.+-。[)SD) of the control after 5 min or 10 min application of halothane, respectively. In some cells (4 out of 15), IPSC was slightly augmented at an early stage (1-2min) of halothane application. Microperfusion of glycine induced an inward current. The amplitude and the duration of this glycine-induced current was enhanced by 2% halothane, and returned to the control value after wash-out.Conclusion : The present study showed that halothane enhances the postsynaptic event in the glycinergic inhibitory transmission. But using exactly the same preparation, we reported that halothane suppressed the overall monosynaptic inhibitory transmission evoked by electrical stimulation of the presynapse. These results indicate that halothane's main site of action in the glycinergic inhibitory transmission is presynapse.