Intravenous anesthetics are more effective than volatile anesthetics on inhibitory pathways in rat hippocampal CA1
Intravenous anesthetics are more effective than volatile anesthetics on inhibitory pathways in rat hippocampal CA1
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DOI：
10.1213/01.ane.0000196536.60320.f9
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发表时间：
2006-03-01
影响因子：
5.7
通讯作者：
Roth, SH
中科院分区：
文献类型：
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作者：
Asahi, T;Hirota, K;Roth, SH
在这项研究中，我们研究了挥发性麻醉药和静脉麻醉药对兴奋性突触传递的影响，包括有和没有反复抑制的情况，以阐明兴奋性突触或抑制性突触是主要的作用靶点。在大鼠海马片上记录CA1区锥体神经元的场群峰电位(FPS)。顺向刺激Schaffer侧支连合纤维(Sch)，测量CA1区诱发的FPS(PS[Sch])。此外，还测定了逆行刺激大鼠海马齿状回(ALV)后，刺激SCH引起的FPS(PS[Alv+Sch])，以产生复发性抑制。观察到七氟醚(0.5%~5%)和异氟烷(0.5%~5%)主要抑制PS[Sch]，对PS[Alv+Sch]也有浓度依赖性的相加抑制作用。计算得到PS[SCH]和PS[AlV+SCH]的半数有效浓度(EC50)分别为5.3%和3.9%(七氟醚)和1.7%和1.1%(异氟烷)。硫喷妥钠(2.0×10~(-5)-5.0×10~(-4)m o l/L)对PS[Sch]和PS[Alv+Sch]均有抑制作用，且呈浓度依赖性。硫喷妥钠对PS[SCH]和PS[AlV+SCH]的EC50值分别为3.4×10~(-4)和5.7×10~(-5)mol/L。异丙酚(2.0×10~(-5)~3.5×10~(-4)mol/L)对PS[Sch]无明显影响，但可降低PS[Alv+Sch]，EC50值为5.1×10~(-4)mol/L。有反复抑制作用的TV麻醉药可被γ-氨基丁酸-A受体拮抗剂甲基荷包牡丹碱拮抗。此外，所有麻醉剂均将反复抑制时间从100ms(七氟醚和异氟醚)延长至400ms(异丙酚)。结果提示，七氟醚和异氟醚主要抑制谷氨酸介导的顺行通路，而硫喷妥钠和异丙酚则增强γ-氨基丁酸-A介导的CA1神经元反复抑制通路，从而进一步证明全身麻醉药的作用机制是药物和通路特异性的。
In this study, we have examined the effects of both volatile and IV general anesthetics on excitatory synaptic transmission, with and without recurrent inhibition, to clarify whether excitatory or inhibitory synapses are the major targets of action. Field population spike amplitudes (fPSs) of CA1 pyramidal neurons were recorded in rat hippocampal slices. Schaffer-collateral-commissural fibers (Sch) were stimulated orthodromically, and the evoked fPSs (PS[Sch]) in CA1 area were measured. In addition, the fPSs (PS[Alv + Sch]) elicited by stimulation of the Sch after antidromic stimulation of the alveus hippocampi (Alv) to produce recurrent inhibition were determined. It was observed that sevoflurane (0.5%-5%) and isoflurane (0.5%-5%) primarily inhibited PS[Sch] and also produced additive inhibition on the PS[Alv+Sch] in a concentration-dependent manner. The calculated 50% effective concentration (EC50) values for PS[Sch] and PS[Alv+Sch] were 5.3 vol% and 3.9 vol% (sevoflurane) and 1.7 vol% and 1.1 vol% (isoflurane), respectively. In comparison, thiopental (2.0 X 10(-5)-5.0 x 10(-4) mol/L) reduced both the PS[Sch] and PS[Alv+Sch] in a concentration-dependent manner. The calculated EC50 values for thiopental on PS[Sch] and PS[Alv+Sch] were 3.4 X 10(-4) and 5.7 X 10(-5) mol/L, respectively. Propofol (2.0 X 10(-5)-3.5 X 10(-4) mol/L) had little effect on the PS[Sch] but reduced PS[Alv+Sch] with a calculated EC50 value of 5.1 X 10(-4) mol/L. The effects of the TV anesthetics with recurrent inhibition were antagonized in the presence of the gamma-aminobutyric acid-A-receptor antagonist bicuculline methiodide. In addition, all anesthetics prolonged recurrent inhibition from 100 ms (sevoflurane and isoflurane) to 400 ms (propofol). The results suggest that sevoflurane and isoflurane inhibit mainly on glutamate-mediated orthodromic pathways, whereas thiopental and propofol enhance gamma-aminobutyric acid-A-mediated recurrent inhibitory pathways in CA1 neurons, thus providing further evidence that the mechanisms of general anesthetics are drug- and pathway-specific.