Effects on synaptic inhibition in the hippocampus do not underlie the amnestic and convulsive properties of the nonimmobilizer 1,2-dichlorohexafluorocyclobutane.
Effects on synaptic inhibition in the hippocampus do not underlie the amnestic and convulsive properties of the nonimmobilizer 1,2-dichlorohexafluorocyclobutane.
复制标题
对海马突触抑制的影响并不是非固定剂 1,2-二氯六氟环丁烷的遗忘和惊厥特性的基础。
DOI：
10.1097/00000542-200407000-00012
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发表时间：
2004
期刊：
影响因子：
8.8
通讯作者：
Pearce,RobertA
中科院分区：
文献类型：
--
作者：
Perouansky,Misha;Pearce,RobertA
研究背景1，2-二氯六氟环丁烷（F6，也称为2N）虽然不能抑制对伤害性刺激的运动反应，但它确实能引起健忘症和癫痫发作。这些发生在0.48和1.3倍，分别是从其脂溶性预测的浓度，导致不动。这些影响的分子和细胞基础尚不清楚。离子型γ-氨基丁酸A型（GABAA）受体受麻醉剂强烈调节，在许多癫痫发作模型中起重要作用。此外，海马体是记忆形成的中心结构，并且容易发生癫痫发作。因此，作者研究了F6对GABAA受体介导的抑制在海马neurons.Methodstransverse海马切片制备年轻（12- 21天）的Sprague-Dawley大鼠的影响。抑制性突触后电流记录海马CA 1区锥体细胞的离子型谷氨酸受体拮抗剂的存在下。F6与浴溶液一起施加。在实验过程中在突触抑制的位置处实现的F6的浓度是使用扩散model.ResultsAt高达75 microm的组织浓度（约5 ×预测的最小肺泡浓度），F6没有可辨别的影响GABA介导的突触电流的振幅或动力学。与此相反，异氟烷，延长了衰减时间常数，这些电流在100微米（约0.3 ×最小肺泡浓度）。ConclusionsAt浓度，括号内的在体内遗忘和惊厥诱导的范围内，F6没有明显的影响，快速突触GABAA受体在海马CA 1锥体神经元。突触GABAA受体能明显区分挥发性麻醉剂和原型非固定剂。麻醉剂和非固定剂的相似体内作用可能由不同的细胞机制介导。
BackgroundAlthough it does not suppress movement in response to noxious stimuli, the nonimmobilizer 1, 2-dichlorohexafluorocyclobutane (F6, also known as 2N) does cause amnesia and seizures. These occur at 0.48 and 1.3 times, respectively, the concentrations that are predicted from its lipid solubility to cause immobility. The molecular and cellular basis of these effects is not known. The ionotropic gamma-aminobutyric acid type A (GABAA) receptor is modulated strongly by anesthetics, and it plays an important role in many seizure models. Also, the hippocampus is a structure central to the formation of memory and is susceptible to seizure generation. The authors therefore investigated the effect of F6 on GABAA receptor-mediated inhibition in hippocampal neurons.MethodsTransverse hippocampal slices were prepared from young (12-to 21-day-old) Sprague-Dawley rats. Inhibitory postsynaptic currents were recorded from hippocampal CA1 pyramidal cells in the presence of ionotropic glutamate receptor antagonists. F6 was applied with the bath solution. The concentration of F6 achieved during the experiment at the location of synaptic inhibition was derived using a diffusion model.ResultsAt tissue concentrations of up to 75 microm (approximately 5 x predicted minimal alveolar concentration), F6 had no discernible effect on either the amplitude or the kinetics of GABA-mediated synaptic currents. Isoflurane, by contrast, prolonged the decay time constant of these currents at 100 microm (approximately 0.3 x minimal alveolar concentration).ConclusionsAt concentrations that bracket the in vivo amnestic and seizure-inducing range, F6 has no discernible effect on fast synaptic GABAA receptors in hippocampal CA1 pyramidal neurons. Synaptic GABAA receptors sharply discriminate between volatile anesthetics and a prototype nonimmobilizer. Similar in vivo effects of anesthetics and nonimmobilizers may be mediated by different cellular mechanisms.