Lukatch H S, MacIver M B
Department of Anesthesia, Stanford University School of Medicine, California 94305-5117, USA.
Anesthesiology. 1996 Jun;84(6):1425-34. doi: 10.1097/00000542-199606000-00019.
Anesthetic depth after barbiturate administration has been correlated with distinct electroencephalogram (EEG) patterns. The current study used a rat neocortical brain slice micro-EEG preparation to investigate synaptic mechanisms underlying thiopental-induced transitions in synchronized neuronal activity.
Concentration-dependent cellular actions of thiopental were investigated in brain slices using specific pharmacologic probes, whole cell patch clamps, and extracellular field recordings. Theta-Like micro-EEG oscillations were elicited in neocortical slices by mimicking subcortical cholinergic and gamma-aminobutyric acid (GABA) afferent input with carbachol (100 microM), a cholinergic agonist, and bicuculline (10 microM) a GABAA antagonist.
In the presence of 20 microM thiopental, micro-EEG slowing from theta (7.3 +/- 0.9 Hz, mean +/- SD, n = 19) to delta frequencies (2.5 +/- 0.5 Hz, n = 11) was associated with a threefold prolongation of inhibitory currents. Burst suppression activity occurred at 50 microM thiopental, and appeared to result from direct activation of GABAA-gated chloride currents, observed with voltage clamp recordings, and mimicked with a direct acting GABAA agonist, muscimol (1 microM). Isoelectric activity occurred at 100 microM thiopental, and likely resulted from reduced glutamatergic transmission, evidenced by depressed excitatory postsynaptic potentials. Glutamatergic excitation was required for burst suppression activity, because glutamate receptor antagonists blocked thiopental-induced bursts; forcing a transition to isoelectric activity.
Thiopental produced a continuum of EEG-like states in brain slices similar to those observed in vivo. The progression of thiopental-induced effects appear to have resulted from specific cellular actions that were recruited in a concentration-dependent manner. Progressive enhancement of synaptic inhibition followed by depression of excitatory transmission led to micro-EEG frequency slowing, burst suppression, and isoelectric activity.
巴比妥类药物给药后的麻醉深度与不同的脑电图（EEG）模式相关。本研究使用大鼠新皮质脑片微脑电图制备技术，来研究硫喷妥钠诱导同步神经元活动转变的突触机制。
使用特定的药理学探针、全细胞膜片钳和细胞外场记录，在脑片中研究硫喷妥钠的浓度依赖性细胞作用。通过用胆碱能激动剂卡巴胆碱（100微摩尔）和GABAA拮抗剂荷包牡丹碱（10微摩尔）模拟皮质下胆碱能和γ-氨基丁酸（GABA）传入输入，在新皮质脑片中诱发类θ微脑电图振荡。
在存在20微摩尔硫喷妥钠的情况下，微脑电图从θ频率（7.3±0.9赫兹，平均值±标准差，n = 19）减慢到δ频率（2.5±0.5赫兹，n = 11）与抑制电流延长三倍相关。在50微摩尔硫喷妥钠时出现爆发抑制活动，似乎是由电压钳记录观察到的GABAA门控氯电流直接激活所致，并用直接作用的GABAA激动剂蝇蕈醇（1微摩尔）模拟。在100微摩尔硫喷妥钠时出现等电活动，可能是由于谷氨酸能传递减少所致，兴奋性突触后电位降低证明了这一点。爆发抑制活动需要谷氨酸能兴奋，因为谷氨酸受体拮抗剂阻断了硫喷妥钠诱导的爆发；促使转变为等电活动。
硫喷妥钠在脑片中产生了一系列类似于体内观察到的脑电图样状态。硫喷妥钠诱导效应的进展似乎是由以浓度依赖性方式募集的特定细胞作用所致。突触抑制的逐渐增强随后是兴奋性传递的抑制，导致微脑电图频率减慢、爆发抑制和等电活动。
