Contrasting synaptic actions of the inhalational general anesthetics isoflurane and xenon
Contrasting synaptic actions of the inhalational general anesthetics isoflurane and xenon
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DOI：
10.1097/00000542-200004000-00024
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发表时间：
2000-04-01
期刊：
影响因子：
8.8
通讯作者：
Franks, NP
中科院分区：
文献类型：
--
作者：
de Sousa, SLM;Dickinson, R;Franks, NP
背景：吸入性全身麻醉药异氟醚和氙发挥作用的机制尚不清楚。此外，令人惊讶的是，很少有定量研究这些药物对中枢突触的影响，几乎没有关于氙作用的信息。方法：异氟醚和氙对γ-氨基丁酸介导的用电压钳技术在自发性培养的大鼠海马神经元上研究了GABA能和谷氨酸能突触，结果：异氟醚对GABA能突触的影响最大，通过抑制性突触后电流使总电荷转移显著增加（在最小肺泡浓度时增加约70%）。这种效应完全由抑制性突触后电流的慢成分的增加介导。在突触能突触，异氟烷的效应较小，但它仍然显著减少总电荷转移（在最小肺泡浓度下约30%）通过兴奋性突触后电流，其中N-甲基-D-天冬氨酸（NMDA）和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）/红藻氨酸受体介导的组分大致同样敏感。氙对GABA能抑制性突触后电流或外源性应用GABA诱发的电流无可测量的影响，但可显著抑制通过兴奋性突触后电流的总电荷转移（在最小肺泡浓度下约60%）。氙选择性地抑制NMDA受体介导的成分的电流，但对AMPA/红藻氨酸受体介导的component.Conclusions的影响不大：对于异氟烷和氙，最重要的目标似乎是突触后，作者的结果表明，异氟烷和氙有非常不同的影响GABA能和谷氨酸能突触传递，这可能是他们不同的药理学概况。
Background: The mechanisms by which the inhalational general anesthetics isoflurane and xenon exert their effects are unknown. Moreover, there have been surprisingly few quantitative studies of the effects of these agents on central synapses, with virtually no information available regarding the actions of xenon.Methods: The actions of isoflurane and xenon on gamma-aminobutyric acid-mediated (GABAergic) and glutamatergic synapses were investigated using voltage-clamp techniques on autaptic cultures of rat hippocampal neurons, a preparation that avoids the confounding effects of complex neuronal networks.Results: Isoflurane exerts its greatest effects on GABAergic synapses, causing a marked increase in total charge transfer (by approximately 70% at minimum alveolar concentration) through the inhibitory postsynaptic current. This effect is entirely mediated by an increase in the slow component of the inhibitory postsynaptic current, At glutamatergic synapses, isoflurane has smaller effects, but it nonetheless significantly reduces the total charge transfer (by approximately 30% at minimum alveolar concentration) through the excitatory postsynaptic current, with the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor-mediated components being roughly equally sensitive. Xenon has no measurable effect on GABAergic inhibitory postsynaptic currents or on currents evoked by exogenous application of GABA, but it substantially inhibits total charge transfer (by approximately 60% at minimum alveolar concentration) through the excitatory postsynaptic current. Xenon selectively inhibits the NMDA receptor-mediated component of the current but has little effect on the AMPA/kainate receptor-mediated component.Conclusions: For both isoflurane and xenon, the most important targets appear to be postsynaptic, The authors' results show that isoflurane and xenon have very different effects on GABAergic and glutamatergic synaptic transmission, and this may account for their differing pharmacologic profiles.