Enflurane directly depresses glutamate AMPA and NMDA currents in mouse spinal cord motor neurons independent of actions on GABAA or glycine receptors
Enflurane directly depresses glutamate AMPA and NMDA currents in mouse spinal cord motor neurons independent of actions on GABAA or glycine receptors
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DOI：
10.1097/00000542-200010000-00032
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发表时间：
2000-10-01
期刊：
影响因子：
8.8
通讯作者：
Kendig, JJ
中科院分区：
文献类型：
--
作者：
Cheng, G;Kendig, JJ
背景：脊髓是一个重要的解剖部位，挥发性物质在此部位发挥作用，防止因有害刺激而发生运动。本研究旨在检验安氟烷直接作用于运动神经元以抑制谷氨酸受体的兴奋性突触传递的假设。方法：对 1 至 4 日龄小鼠脊髓切片中视觉识别的运动神经元进行全细胞记录。兴奋性突触后电流（EPSC）或电位（EPSP）是通过电刺激背根进入区或背角引起的。通过使用选择性拮抗剂，EPSC 在药理学上被分离成谷氨酸 N-甲基-D-天冬氨酸 (NMDA) 受体介导的成分和非 NMDA 受体介导的成分。在不同的药理阻断条件下，谷氨酸的短暂脉冲压力喷射也会引起电流。将安氟醚配制为饱和储备溶液，并在上清液中稀释；结果：通过刺激背角从运动神经元记录的兴奋性突触后电流和 EPSP 由非 NMDA 和 NMDA 亚型的谷氨酸受体介导。安氟烷在全身麻醉浓度（一种最低肺泡麻醉浓度）下可逆性抑制 EPSC 和 EPSP。在河豚毒素 (300 nM) 存在的情况下，安氟烷还能抑制谷氨酸诱发的电流，表明其作用是突触后的。用荷包牡丹碱（20μM）或马钱子碱（2μM）或两者阻断抑制性γ-氨基丁酸A和甘氨酸受体并没有显着降低安氟醚对谷氨酸诱发电流的影响。如果阻断抑制性受体，并且分别应用 D,L-2-氨基-5-膦基戊酸 (50 μM) 或 6-氰基-7-硝基喹喔啉-2,3-二酮二钠 (10 μM) 阻断 NMDA 或 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸-红藻氨酸受体，安氟烷也会抑制谷氨酸诱发电流。 Enflurane 对运动神经元中的 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸和 NMDA 谷氨酸电流产生直接抑制作用。这种效果不需要增强γ-氨基丁酸A和甘氨酸抑制作用。因此，通过对运动神经元的突触后作用直接抑制谷氨酸能兴奋性传递，可能有助于全身麻醉，如响应有害刺激而不动所定义的。
Background: The spinal cord is an important anatomic site at which volatile agents act to prevent movement in response to a noxious stimulus. This study was designed to test the hypothesis that enflurane acts directly on motor neurons to inhibit excitatory synaptic transmission at glutamate receptors.Methods: Whole-cell recordings were made in visually identified motor neurons in spinal cord slices from 1- to 4-day-old mice. Excitatory postsynaptic currents (EPSCs) or potentials (EPSPs) were evoked by electrical stimulation of the dorsal root entry area or dorsal horn. The EPSCs were isolated pharmacologically into glutamate N-methyl-D-aspartate (NMDA) receptor- and non-NMDA receptor-mediated components by using selective antagonists. Currents also were evoked by brief pulse pressure ejection of glutamate under various conditions of pharmacologic blockade. Enflurane was made up as a saturated stock solution and diluted In the superfusate; concentrations were measured using gas chromatography.Results: Excitatory postsynaptic currents and EPSPs recorded from motor neurons by stimulation in the dorsal horn were mediated by glutamate receptors of both non-NMDA and NMDA subtypes. Enflurane at a general anesthetic concentration (one minimum alveolar anesthetic concentration) reversibly depressed EPSCs and EPSPs. Enflurane also depressed glutamate-evoked currents in the presence of tetrodotoxin (300 nM), showing that its actions are postsynaptic. Block of inhibitory gamma-aminobutyric acid A and glycine receptors by bicuculline (20 mu M) or strychnine (2 mu M) or both did not significantly reduce the effects of enflurane on glutamate-evoked currents. Enflurane also depressed glutamate-evoked currents if the inhibitory receptors were blocked and if either D,L-2-amino-5-phosphonopentanoic acid (50 mu M) or 6-cyano-7-nitroquinoxaline-2,3-dione disodium (10 mu M) was applied to block NMDA or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-kainate receptors respectivelyConclusions: Enflurane exerts direct depressant effects on both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and NMDA glutamate currents in motor neurons. Enhancement of gamma-aminobutyric acid A and glycine inhibition is not needed for this effect Direct depression of glutamatergic excitatory transmission by a postsynaptic action on motor neurons thus may contribute to general anesthesia as defined by immobility in response to a noxious stimulus.