Anesthetic-induced burst suppression EEG activity requires glutamate-mediated excitatory synaptic transmission
Anesthetic-induced burst suppression EEG activity requires glutamate-mediated excitatory synaptic transmission
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DOI：
10.1093/cercor/bhi015
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发表时间：
2005-09-01
期刊：
影响因子：
3.7
通讯作者：
MacIver, MB
中科院分区：
文献类型：
--
作者：
Lukatch, HS;Kiddoo, CE;MacIver, MB
许多麻醉药在麻醉期间引起人和动物的脑电图（EEG）爆发抑制活动，这种活动的机制尚不清楚。本研究采用大鼠脑皮层脑电切片，探讨麻醉诱发的爆发抑制活动的兴奋性突触机制。利用谷氨酸受体拮抗剂（CNQX和APV）、GABA受体拮抗剂、全细胞膜片钳和微电极脑电图同时记录，探索与爆发抑制活性相关的兴奋性突触机制。临床相关浓度的硫喷妥钠（50-70 μ M）、异丙酚（5-10 μ M）或异氟醚（0.7-2.1 vol%, 0.5-1.5大鼠最低平均浓度（MAC）， 200-700 μ M）诱发的δ慢波活动和爆发抑制脑电图模式与体内反应相似。谷氨酸受体拮抗剂CNQX （8.6 μ M）或APV （50 μ M）可阻断其对脑电图信号的影响。去极化细胞内爆发（振幅= 34.7 +/- 4.5 mV，半宽= 132 +/- 60 ms）总是伴随着脑电图爆发，超极化增加了细胞内爆发振幅。谷氨酸介导的兴奋事件引发脑电图爆发活动。高麻醉浓度显著抑制了谷氨酸介导的兴奋性突触后电流，从而抑制了脉冲抑制性脑电图活动。GABA(A)激动剂产生与麻醉剂相似的脑电图效应。似乎麻醉作用在谷氨酸和GABA突触都有助于麻醉期间看到的脑电图模式。
Many anesthetics evoke electroencephalogram (EEG) burst suppression activity in humans and animals during anesthesia, and the mechanisms underlying this activity remain unclear. The present study used a rat neocortical brain slice EEG preparation to investigate excitatory synaptic mechanisms underlying anesthetic-induced burst suppression activity. Excitatory synaptic mechanisms associated with burst suppression activity were probed using glutamate receptor antagonists (CNQX and APV), GABA receptor antagonists, and simultaneous whole cell patch clamp and microelectrode EEG recordings. Clinically relevant concentrations of thiopental (50-70 mu M), propofol (5-10 mu M) or isoflurane (0.7-2.1 vol%, 0.5-1.5 rat minimum aveolar concentration (MAC), 200-700 mu M) evoked delta slow wave activity and burst suppression EEG patterns similar to in vivo responses. These effects on EEG signals were blocked by glutamate receptor antagonists CNQX (8.6 mu M) or APV (50 mu M). Depolarizing intracellular bursts (amplitude = 34.7 +/- 4.5 mV; half width = 132 +/- 60 ms) always accompanied EEG bursts, and hyperpolarization increased intracellular burst amplitudes. Barrages of glutamate-mediated excitatory events initiated EEG bursting activity. Glutamate-mediated excitatory postsynaptic currents were significantly depressed by higher anesthetic concentrations that depressed burst suppression EEG activity. A GABA(A) agonist produced a similar EEG effect to the anesthetics. It appears that anesthetic effects at both glutamate and GABA synapses contribute to EEG patterns seen during anesthesia.