Yamamura T, Harada K, Okamura A, Kemmotsu O
Department of Anesthesiology, Hokkaido University School of Medicine, Sapporo, Japan.
Anesthesiology. 1990 Apr;72(4):704-10. doi: 10.1097/00000542-199004000-00021.
Synaptic mechanisms underlying ketamine anesthesia were studied using in vitro preparations of the lamprey CNS. Although lampreys are one of the most primitive vertebrates, the synaptic physiology and pharmacology are similar to those in the higher vertebrates. Axonal conduction, transmitter release from the presynaptic terminal, postsynaptic response to the putative neurotransmitters, and resting and activated membrane properties were studied in the absence and the presence of various concentrations of ketamine. Ketamine markedly reduced N-methyl-D-aspartate (NMDA)-activated responses, such as depolarizations to bath-applied NMDA and bursting rhythm during "fictive locomotion." The 50% block of the responses took place in the presence of 10-20 microM ketamine, whereas those induced by kainate and quisqualate (the other two subclasses of L-glutamate/L-aspartate agonists) were spared at concentrations higher than 600-800 microM. None of the other neuronal events tested were suppressed in the presence of still higher concentrations of ketamine. The results support the hypothesis that ketamine might exert its anesthetic effect by a pharmacologically specific interaction with the NMDA receptor.
使用七鳃鳗中枢神经系统的体外制备物研究了氯胺酮麻醉的突触机制。尽管七鳃鳗是最原始的脊椎动物之一，但其突触生理学和药理学与高等脊椎动物相似。在不存在和存在不同浓度氯胺酮的情况下，研究了轴突传导、突触前终末的递质释放、对假定神经递质的突触后反应以及静息和激活的膜特性。氯胺酮显著降低了N-甲基-D-天冬氨酸（NMDA）激活的反应，如对浴槽施加NMDA的去极化和“虚拟运动”期间的爆发节律。在存在10-20微摩尔氯胺酮的情况下，反应出现50%的阻断，而由 kainate 和 quisqualate（L-谷氨酸/L-天冬氨酸激动剂的另外两个亚类）诱导的反应在高于600-800微摩尔的浓度下不受影响。在存在更高浓度氯胺酮的情况下，所测试的其他神经元事件均未受到抑制。这些结果支持了氯胺酮可能通过与NMDA受体发生药理学特异性相互作用来发挥其麻醉作用的假说。
