Talavera Jason A, Esser Steven K, Amzica Florin, Hill Sean, Antognini Joseph F
Department of Anesthesiology and Pain Medicine, University of California, Davis, CA 95616, USA.
Anesth Analg. 2009 Jan;108(1):160-7. doi: 10.1213/ane.0b013e31818d40aa.
We have used a computational model of the thalamocortical system to investigate the effects of a GABAergic anesthetic (etomidate) on cerebral cortical and thalamic neuronal function. We examined the effects of phasic and tonic inhibition, as well as the relative importance of anesthetic action in the thalamus and cortex.
The amount of phasic GABAergic inhibition was adjusted in the model to simulate etomidate concentrations of between 0.25 and 2 microM, with the concentration range producing unconsciousness assumed to be between 0.25 and 0.5 microM. In addition, we modeled tonic inhibition separately, and then phasic and tonic inhibition together. We also introduced phasic and tonic inhibition into the cerebral cortex and thalamus separately to determine the relative importance of each of these structures to anesthetic-induced depression of the thalamocortical system.
Phasic inhibition decreased cortical neuronal firing by 11%-18% in the 0.25-0.5 microM range and by 38% at 2 microM. Tonic inhibition produced similar depression (11%-21%) in the 0.25-0.5 microM range but 65% depression at 2 microM; phasic and tonic inhibition combined produced the most inhibition (76% depression at 2 microM). When the thalamus and cortex were separately subjected to phasic and tonic inhibition, cortical firing rates decreased less compared to when both structures were targeted. In the 0.25-0.5 microM range, cortical firing rate was minimally affected when etomidate action was simulated in the thalamus only.
This computational model of the thalamocortical system indicated that tonic GABAergic inhibition seems to be more important than phasic GABAergic inhibition (especially at larger etomidate concentrations), although both combined had the most effect on cerebral cortical firing rates. Furthermore, etomidate action in the thalamus, by itself, does not likely explain etomidate-induced unconsciousness.
我们使用了一个丘脑皮质系统的计算模型来研究γ-氨基丁酸（GABA）能麻醉剂（依托咪酯）对大脑皮质和丘脑神经元功能的影响。我们研究了相位性和紧张性抑制的作用，以及麻醉作用在丘脑和皮质中的相对重要性。
在模型中调整相位性GABA能抑制的量，以模拟0.25至2微摩尔浓度的依托咪酯，假定产生无意识状态的浓度范围为0.25至0.5微摩尔。此外，我们分别对紧张性抑制进行建模，然后对相位性和紧张性抑制一起建模。我们还分别将相位性和紧张性抑制引入大脑皮质和丘脑，以确定这些结构中每一个对麻醉诱导的丘脑皮质系统抑制的相对重要性。
在0.25至0.5微摩尔范围内，相位性抑制使皮质神经元放电减少11%至18%，在2微摩尔时减少38%。紧张性抑制在0.25至0.5微摩尔范围内产生类似的抑制作用（11%至21%），但在2微摩尔时抑制作用达65%；相位性和紧张性抑制共同作用产生的抑制作用最强（在2微摩尔时抑制76%）。当丘脑和皮质分别受到相位性和紧张性抑制时，与两个结构都受到靶向作用相比，皮质放电率下降较少。在0.25至0.5微摩尔范围内，仅在丘脑模拟依托咪酯作用时，皮质放电率受影响最小。
这个丘脑皮质系统的计算模型表明，紧张性GABA能抑制似乎比相位性GABA能抑制更重要（特别是在较高的依托咪酯浓度下），尽管两者共同作用对大脑皮质放电率的影响最大。此外，依托咪酯在丘脑中的作用本身不太可能解释依托咪酯诱导的无意识状态。
