Perouansky M, Baranov D, Salman M, Yaari Y
Department of Anesthesiology and Critical Care, Hadassah University Hospital-Hebrew University, Jerusalem, Israel.
Anesthesiology. 1995 Jul;83(1):109-19. doi: 10.1097/00000542-199507000-00014.
The effects of halothane on excitatory synaptic transmission in the central nervous system of mammals have been studied in vivo and in vitro in several investigations with partially contradicting results. Direct measurements of the effects of halothane on isolated glutamate receptor-mediated (glutamatergic) excitatory postsynaptic currents (EPSCs), however, have not been reported to date.
The effects of halothane on glutamatergic EPSCs were studied in vitro by using tight-seal, whole-cell recordings from CA1 pyramidal cells in thin slices from the adult mouse hippocampus. The EPSCs were pharmacologically isolated into their non-N-methyl-D-aspartate (non-NMDA) and NMDA receptor-mediated components by using selective antagonists. The effects of halothane on EPSC amplitude and kinetics were analyzed at various membrane potentials and were compared with its effects on currents evoked by exogenously applied glutamatergic agonists.
Halothane (0.2-5.1%; 0.37-2.78 mM) reversibly blocked non-NMDA and NMDA EPSCs. This effect was voltage independent; concentrations producing 50% inhibition were 0.87% (0.66 mM) and 0.69% (0.57 mM), respectively. Currents induced by bath-applied glutamatergic agonists were not affected even by the high concentrations of halothane.
Halothane depresses glutamatergic EPSCs irrespective of receptor subtype, most likely by inhibition of glutamate release.
在几项体内和体外研究中,已对氟烷对哺乳动物中枢神经系统兴奋性突触传递的影响进行了研究,但结果部分相互矛盾。然而,迄今为止,尚未有关于氟烷对分离的谷氨酸受体介导的(谷氨酸能)兴奋性突触后电流(EPSC)影响的直接测量报告。
通过使用成年小鼠海马薄片中CA1锥体细胞的全细胞膜片钳记录,在体外研究氟烷对谷氨酸能EPSC的影响。使用选择性拮抗剂将EPSC药理学分离为其非N-甲基-D-天冬氨酸(非NMDA)和NMDA受体介导的成分。在不同膜电位下分析氟烷对EPSC幅度和动力学的影响,并将其与对外源施加的谷氨酸能激动剂诱发电流的影响进行比较。
氟烷(0.2 - 5.1%;0.37 - 2.78 mM)可逆地阻断非NMDA和NMDA EPSC。这种作用与电压无关;产生50%抑制的浓度分别为0.87%(0.66 mM)和0.69%(0.57 mM)。即使是高浓度的氟烷也不会影响浴应用谷氨酸能激动剂诱发的电流。
氟烷抑制谷氨酸能EPSC,与受体亚型无关,最可能是通过抑制谷氨酸释放。