Wakasugi M, Hirota K, Roth S H, Ito Y
Department of Anesthesiology, Toyama Medical and Pharmaceutical University School of Medicine, Japan.
Anesth Analg. 1999 Mar;88(3):676-80. doi: 10.1097/00000539-199903000-00039.
It is unclear whether general anesthetics induce enhancement of neural inhibition and/or attenuation of neural excitation. We studied the effects of pentobarbital (5 x 10(-4) mol/L), propofol (5 x 10(-4) mol/L), ketamine (10(-3) mol/L), halothane (1.5 vol%), and isoflurane (2.0 vol%) on both excitatory and inhibitory synaptic transmission in rat hippocampal slices. Excitatory or inhibitory synaptic pathways were isolated using pharmacological antagonists. Extracellular microelectrodes were used to record electrically evoked CA1 neural population spikes (PSs). In the presence of the gamma-aminobutyric acid type A (GABA(A)) receptor antagonist (bicuculline), the inhibitory actions of pentobarbital and propofol were completely antagonized, whereas those of ketamine, halothane, and isoflurane were only partially blocked. To induce the N-methyl-D-aspartate (NMDA) receptor-mediated PS (NMDA PS), the non-NMDA and GABA(A) receptors were blocked in the absence of Mg2+. Ketamine, halothane, and isoflurane decreased the NMDA PS, and pentobarbital and propofol had no effect on the NMDA PS. The non-NMDA receptor-mediated PS (non-NMDA PS) was examined using the antagonists for the NMDA and GABA(A) receptors. Volatile, but not i.v., anesthetics reduced the non-NMDA PS. These findings indicate that pentobarbital and propofol produce inhibitory actions due to enhancement in the GABA(A) receptor; that ketamine reduces NMDA receptor-mediated responses and enhances GABA(A) receptor-mediated responses; and that halothane and isoflurane modulate GABA(A), NMDA, and non-NMDA receptor-mediated synaptic transmission.
Volatile anesthetics modulate both excitatory and inhibitory synaptic transmission of in vitro rat hippocampal pathways, whereas i.v. anesthetics produce more specific actions on inhibitory synaptic events. These results provide further support the idea that general anesthetics produce drug-specific and distinctive effects on different pathways in the central nervous system.
全身麻醉药是否会增强神经抑制和/或减弱神经兴奋尚不清楚。我们研究了戊巴比妥（5×10⁻⁴mol/L）、丙泊酚（5×10⁻⁴mol/L）、氯胺酮（10⁻³mol/L）、氟烷（1.5体积%）和异氟烷（2.0体积%）对大鼠海马切片中兴奋性和抑制性突触传递的影响。使用药理学拮抗剂分离兴奋性或抑制性突触通路。细胞外微电极用于记录电诱发的CA1神经群体锋电位（PSs）。在存在γ-氨基丁酸A型（GABA(A)）受体拮抗剂（荷包牡丹碱）的情况下，戊巴比妥和丙泊酚的抑制作用被完全拮抗，但氯胺酮、氟烷和异氟烷的抑制作用仅被部分阻断。为了诱导N-甲基-D-天冬氨酸（NMDA）受体介导的PS（NMDA PS），在无镁离子的情况下阻断非NMDA和GABA(A)受体。氯胺酮、氟烷和异氟烷降低了NMDA PS，而戊巴比妥和丙泊酚对NMDA PS无影响。使用NMDA和GABA(A)受体拮抗剂检测非NMDA受体介导的PS（非NMDA PS）。挥发性麻醉药而非静脉麻醉药降低了非NMDA PS。这些发现表明，戊巴比妥和丙泊酚由于GABA(A)受体增强而产生抑制作用；氯胺酮降低NMDA受体介导的反应并增强GABA(A)受体介导的反应；氟烷和异氟烷调节GABA(A)、NMDA和非NMDA受体介导的突触传递。
挥发性麻醉药调节体外大鼠海马通路的兴奋性和抑制性突触传递，而静脉麻醉药对抑制性突触事件产生更具特异性的作用。这些结果进一步支持了全身麻醉药对中枢神经系统不同通路产生药物特异性和独特作用的观点。
