Astrocytes contribute to the effects of etomidate on synaptic transmission in rat primary somatosensory cortex.
Astrocytes contribute to the effects of etomidate on synaptic transmission in rat primary somatosensory cortex.
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星形胶质细胞有助于依托咪酯对大鼠初级体感皮层突触传递的影响。
DOI：
10.1016/j.brainres.2016.03.052
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发表时间：
2016
期刊：
影响因子：
2.9
通讯作者：
Yu Tian
中科院分区：
文献类型：
--
作者：
Yang Hao;Wang Yuan;Zhang Yu;Zhang You;Xu Mao-Sheng;Yuan Jie;Yu Tian
目前对全麻药致意识障碍的机制知之甚少。以往的研究表明，初级躯体感觉皮层(S1)是一种对多种静脉全身麻醉药敏感的区域。依托咪酯是一种广泛使用的静脉麻醉剂，可影响突触传递。最近有证据表明，星形胶质细胞作为一种神经胶质细胞，也参与脑内信息传递，并通过释放神经活性物质来调节突触功能。然而，尚不清楚星形胶质细胞是否影响依托咪酯对S1锥体神经元信息传递的影响。本研究采用全细胞膜片钳技术研究了星形胶质细胞在依托咪酯致意识障碍中的作用。我们观察到临床相关浓度依托咪酯对大鼠S1锥体神经元自发突触后电流(SPSCs)的抑制作用呈浓度依赖性，量效曲线显示依托咪酯抑制sPSCs的EC50值为6.9μM。此外，在阻断乌头酸酶的神经胶质细胞选择性代谢抑制剂氟柠檬酸存在下，sPSCs的幅度和频率均降低，依托咪酯对sPSCs幅度的抑制作用增强，但不影响依托咪酯对频率的影响。根据这些数据，我们推断依托咪酯通过突触前和突触后成分抑制突触活动。此外，星形胶质细胞参与突触传递，并影响依托咪酯对突触后受体的影响。这项研究为星形胶质细胞在依托咪酯诱导的意识丧失中所起的作用提供了新的见解。
Little is known about the mechanisms of unconsciousness induced by general anesthetics. Previous studies have shown that the primary somatosensory cortex (S1) is a sensitive region to a variety of intravenous general anesthetics. Etomidate is a widely used intravenous anesthetic that can influence synaptic transmission. Recently, there are some evidences suggesting that astrocytes, a type of glia cell, also contribute to information transmission in the brain, and modulate synaptic function by releasing neuroactive substances. However, it is unknown whether astrocytes influence the effects of etomidate on information transmission in S1 pyramidal neurons. In the present study, the role of astrocytes in etomidate-induced unconsciousness was investigated by using the whole-cell patch clamp technique. We observed etomidate at clinically relevant concentrations inhibited the spontaneous postsynaptic currents (sPSCs) of rat S1 pyramidal neurons in a concentration-dependent manner, and the EC50 value of etomidate for inhibiting sPSCs from the concentration-effect curve was 6.9 μM. Furthermore, in the presence of fluorocitrate, a glia-selective metabolism inhibitor that blocks the aconitase enzyme, both the amplitude and frequency of sPSCs in rat S1 pyramidal neurons were reduced, and the inhibitory effects of etomidate on sPSCs amplitude was strengthened without affecting the effects of etomidate on frequency. From these data, we deduce that etomidate suppresses synaptic activity via presynaptic and postsynaptic components. Furthermore, astrocytes participate in synaptic transmission and influence the effects of etomidate on postsynaptic receptors. This study provides new insight into the role of astrocytes in etomidate-induced unconsciousness.