Etomidate Modulates the Tactile Stimulation-Evoked Field Potential Responses in Cerebellar Granule Cell Layer in vivo in Mice
Etomidate Modulates the Tactile Stimulation-Evoked Field Potential Responses in Cerebellar Granule Cell Layer in vivo in Mice
复制标题
依托咪酯调节小鼠体内小脑颗粒细胞层触觉刺激诱发的场电位反应
DOI：
10.1159/000502133
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发表时间：
2019
期刊：
影响因子：
3.1
通讯作者：
De-Lai Qiu
中科院分区：
文献类型：
--
作者：
Wen Pan;Li-Na Cui;Chun-Ping Chu;Wen-Zhe Jin;De-Lai Qiu
依托咪酯(ET)通过与γ-氨基丁酸A型(GABAA)受体结合产生镇静作用。我们先前在小鼠体内发现，ET通过GABAA和甘氨酸受体抑制小脑浦肯野细胞的活动，提示ET调节小脑皮质感觉信息的突触传递。本研究采用电生理学和药理学方法，观察ET对乌拉坦麻醉小鼠小脑颗粒层(GL)感觉刺激诱发反应的影响。结果表明，小脑表面灌流ET(100μ/L)可显著降低小脑GL的感觉兴奋成分(N1)的幅度和曲线下面积(AUC)。应用GABAA受体拮抗剂SR95531(20μ/L)可显著减弱但不能消除ET引起的面部刺激诱发反应的波幅和AUC值的降低。但应用SR95531(20μm ol/L)和大麻素1受体拮抗剂AM-251(5μm ol/L)的混合液，可完全阻断ET引起的面部刺激诱发反应的幅度和AUC值的降低。此外，应用CB1受体激动剂WIN55212-2，在没有GABAA受体活性的情况下，N1的幅度和AUC降低，并阻断ET诱导的N1的抑制。此外，在缺乏GABAA受体活性的情况下，ET引起的N1的幅度和AUC的变化可被特异性蛋白激酶A(PKA)抑制剂KT5720取消。这些结果表明，在GABAA受体缺乏活性的情况下，ET可使CB1受体易化，从而通过PKA信号通路抑制感觉刺激诱发的突触传递。
Etomidate (ET) produces sedation by binding on the γ-aminobutyric acid type A (GABA A) receptors. We previously found that ET inhibited cerebellar Purkinje cells activity via both GABA A and glycine receptors in vivo in mice, suggesting that ET modulated sensory information synaptic transmission in cerebellar cortex. In this study, we investigated the effect of ET on the sensory stimulation-evoked responses in the cerebellar granule layer (GL) in urethane-anesthetized mice, using electrophysiological and pharmacological methods. Our results showed that cerebellar surface perfusion of ET (100 μmol/L) significantly decreased amplitude and area under the curve (AUC) of the sensory stimulation-evoked excitatory component (N1) in the cerebellar GL. Application of GABA A receptor antagonist, SR95531 (20 μmol/L) significantly attenuated, but not abolished the ET-induced decrease in amplitude and AUC of facial stimulation-evoked responses. However, application of a mixture of SR95531 (20 μmol/L) and cannabinoid 1 receptor (CB1) antagonist, AM-251 (5 μmol/L), completely blocked the ET-induced decrease in amplitude and AUC of facial stimulation-evoked responses. Furthermore, application of the CB1 receptor agonist, WIN55212-2, induced a decrease in amplitude and AUC of N1 in the absence of GABA A receptors activity, as well occluded the ET-induced depression of N1. Moreover, the ET-induced changes in amplitude and AUC of N1 in absence of GABA A receptors activity were abolished by a specific protein kinase A (PKA) inhibitor, KT5720. These results indicate that ET facilitates CB1 receptors in the absence of GABA A receptors activity, resulting in a depression of the sensory stimulation-evoked synaptic transmission via PKA signaling pathway in mouse cerebellar GL.