Zhang Yu, Wu Sisi, Xie Liwei, Yu Shouyang, Zhang Lin, Liu Chengxi, Zhou Wenjing, Yu Tian
Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Guizhou, China.
The Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University, Guizhou, China.
Front Cell Neurosci. 2019 Jun 11;13:240. doi: 10.3389/fncel.2019.00240. eCollection 2019.
Astrocytes are now considered as crucial modulators of neuronal synaptic transmission. General anesthetics have been found to inhibit astrocytic activities, but it is not clear whether general anesthetics within the clinical concentration range affects the astrocyte-mediated synaptic regulation.
The effects of propofol, dexmedetomidine, and ketamine within clinically effective ranges on the slow inward currents (SICs) were tested by using the whole-cell recording in acute prefrontal cortex (PFC) slice preparations of rats. Astrocytes culture and HPLC were used to measure the effects of different anesthetics on the glutamate release of astrocytes.
Propofol and dexmedetomidine showed no significant effect on the amplitude or frequency of SICs. Ketamine was found to inhibit the frequency of SICs in a concentration-dependent manner. The SICs synchronization rate of paired neurons was inhibited by 30 μM ketamine (from 42.5 ± 1.4% to 9.6 ± 0.8%) and was abolished by 300 μM ketamine. The astrocytic glutamate release induced by DHPG, an agonist of astrocytic type I metabotropic glutamate receptors, was not affected by ketamine, and ifenprodil, a selective antagonist of GluN1/GluN2B receptor, blocked all SICs and enhanced the inhibitory effect of 30 μM ketamine on the frequency of SICs. Ketamine at low concentration (3 μM) could inhibit the frequency of SICs, not the miniature excitatory postsynaptic currents (mEPSCs), and the inhibition rate of SICs was significantly higher than mEPSCs with 30 μM ketamine (44.5 ± 3% inhibition vs. 28.3 ± 6% inhibition).
Our data indicated that ketamine, not propofol and dexmedetomidine, within clinical concentration range inhibits glutamatergic transmission from astrocytes to neurons, which is likely mediated by the extrasynaptic GluN1/GluN2B receptor activation.
星形胶质细胞现在被认为是神经元突触传递的关键调节因子。已发现全身麻醉药会抑制星形胶质细胞的活动，但尚不清楚临床浓度范围内的全身麻醉药是否会影响星形胶质细胞介导的突触调节。
通过在大鼠急性前额叶皮质（PFC）脑片制备物中进行全细胞记录，测试了临床有效范围内的丙泊酚、右美托咪定和氯胺酮对慢内向电流（SICs）的影响。采用星形胶质细胞培养和高效液相色谱法来测量不同麻醉药对星形胶质细胞谷氨酸释放的影响。
丙泊酚和右美托咪定对SICs的幅度或频率无显著影响。发现氯胺酮以浓度依赖性方式抑制SICs的频率。30 μM氯胺酮可抑制配对神经元的SICs同步率（从42.5±1.4%降至9.6±0.8%），300 μM氯胺酮可消除该同步率。星形胶质细胞I型代谢型谷氨酸受体激动剂DHPG诱导的星形胶质细胞谷氨酸释放不受氯胺酮影响，而GluN1/GluN2B受体选择性拮抗剂ifenprodil可阻断所有SICs并增强30 μM氯胺酮对SICs频率的抑制作用。低浓度（3 μM）氯胺酮可抑制SICs的频率，但不影响微小兴奋性突触后电流（mEPSCs），且30 μM氯胺酮对SICs的抑制率显著高于mEPSCs（抑制率分别为44.5±3%和28.3±6%）。
我们的数据表明，临床浓度范围内的氯胺酮而非丙泊酚和右美托咪定可抑制从星形胶质细胞到神经元的谷氨酸能传递，这可能是由突触外GluN1/GluN2B受体激活介导的。
