【罂粟摘要】星形胶质细胞中的GABA A受体是常用的静脉和吸入全麻药物的作用靶点

星形胶质细胞中的GABA A受体是常用的静脉和吸入全麻药物的作用靶点

贵州医科大学 麻醉与心脏电生理课题组

翻译：严旭  编辑：马艳燕  审校：曹莹

 寒 露 寒露 COLD DEW

背景：

围手术期神经认知障碍（PNDs）通常发生在麻醉和手术后的老年患者中。用全身麻醉药物治疗星形胶质细胞会刺激可溶性因子的释放，增加神经元中GABAA受体的细胞表面表达和功能。然而，这种干扰可能有助于治疗PNDs；麻醉药物在星形胶质细胞中的作用靶点还没有被确定。GABAA受体是全身麻醉药物在神经元中的主要靶点，也在星形胶质细胞中表达，这使这些药物有可能作用于星形胶质细胞中的GABAA受体，从而引发可溶性因子的释放。到目前为止，还没有研究直接考察星形细胞中的GABAA受体对临床上经常使用的全身麻醉药物的敏感性。因此，本研究的目的是确定星形细胞中GABAA受体的功能是否受到静脉麻醉剂依托咪酯和吸入麻醉剂七氟烷的调节。

方法：

对来自C57BL/6雄性小鼠的海马CA1区的星形细胞进行全细胞电压记录。通过形态学和电生理学特性识别星形胶质细胞。用皮科斯普利策系统对GABA（300μM）进行病灶扑击，以诱发GABA反应。在应用非竞争性GABAA受体拮抗剂微量元素（0.5mM），依托咪酯（100μM）或七氟烷（532μM）之前和期间监测了电流。

结果：

GABA持续诱发内向电流，并被微量元素抑制。依托咪酯使峰值电流的振幅增加了35.0±24.4%，衰减时间延长了27.2±24.3%（n = 7，P < 0.05）。七氟烷使电流衰减时间延长了28.3 ± 23.1%（n = 7，P < 0.05），但没有改变峰值振幅。依托咪酯和七氟烷使电荷转移（面积）分别增加了71.2±45.9%和51.8±48.9%（n = 7，P < 0.05）。

结论：

依托咪酯和七氟烷可以增加海马中星形胶质细胞中GABAA受体的功能。未来将继续研究这些全身麻醉药物是否作用于星形细胞的GABAA受体，从而刺激PNDs的可溶性因子释放。

原始文献来源：

Woosuk Chung,  Dian-Shi Wang , Shahin Khodaei, 1 Arsene Pinguelo,   Beverley A. Orser 

GABAAReceptors in Astrocytes Are Targets for Commonly Used Intravenous and Inhalational General Anesthetic Drugs Front Aging Neurosci. 2021; 13: 802582. 

寒露 COLD DEW

GABAA Receptors in Astrocytes Are Targets for Commonly Used Intravenous and Inhalational General Anesthetic Drugs

Background: 

Perioperative neurocognitive disorders (PNDs) occur commonly in older patients after anesthesia and surgery. Treating astrocytes with general anesthetic drugs stimulates the release of soluble factors that increase the cell-surface expression and function of GABAAreceptors in neurons. Such crosstalk may contribute to PNDs; however, the receptor targets in astrocytes for anesthetic drugs have not been identified. GABAA receptors, which are the major targets of general anesthetic drugs in neurons, are also expressed in astrocytes, raising the possibility that these drugs act on GABAA receptors in astrocytes to trigger the release of soluble factors. To date, no study has directly examined the sensitivity of GABAA receptors in astrocytes to general anesthetic drugs that are frequently used in clinical practice. Thus, the goal of this study was to determine whether the function of GABAA receptors in astrocytes was modulated by the intravenous anesthetic etomidate and the inhaled anesthetic sevoflurane. 

Methods: 

Whole-cell voltage-clamp recordings were performed in astrocytes in the stratum radiatum of the CA1 region of hippocampal slices isolated from C57BL/6 male mice. Astrocytes were identified by their morphologic and electrophysiologic properties. Focal puff application of GABA (300 μM) was applied with a Picospritzer system to evoke GABA responses. Currents were studied before and during the application of the non-competitive GABAA receptor antagonist picrotoxin (0.5 mM), or etomidate (100 μM) or sevoflurane (532 μM). 

Results: 

GABA consistently evoked inward currents that were inhibited by picrotoxin. Etomidate increased the amplitude of the peak current by 35.0 ± 24.4% and prolonged the decay time by 27.2 ± 24.3% (n = 7, P < 0.05). Sevoflurane prolonged current decay by 28.3 ± 23.1% (n = 7, P < 0.05) but did not alter the peak amplitude. Etomidate and sevoflurane increased charge transfer (area) by 71.2 ± 45.9% and 51.8 ± 48.9% (n = 7, P < 0.05), respectively. 

Conclusion:

 The function of astrocytic GABAA receptors in the hippocampus was increased by etomidate and sevoflurane. Future studies will determine whether these general anesthetic drugs act on astrocytic GABAA receptors to stimulate the release of soluble factors that may contribute to PNDs.

打赏