Presynaptic and postsynaptic actions of halothane at glutamatergic synapses in the mouse hippocampus
Presynaptic and postsynaptic actions of halothane at glutamatergic synapses in the mouse hippocampus
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DOI：
10.1038/sj.bjp.0701996
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发表时间：
1998-08-01
影响因子：
7.3
通讯作者：
Perouansky, M
中科院分区：
文献类型：
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作者：
Kirson, ED;Yaari, Y;Perouansky, M
1 使用成年小鼠海马切片的全细胞膜片钳记录来测试挥发性麻醉剂氟烷抑制谷氨酸受体介导的突触传递的机制。 CA1 锥体细胞中的非 N-甲基-D-天冬氨酸 (nonNMDA) 和 NMDA 受体介导的电流分别通过 D,L-2-氨基-5-磷酸戊酸 (APV；100 μM) 或 6-氰基-7-硝基-喹喔啉-2,3-二酮 (CNQX；5 μM) 的浴应用进行药理学分离。2 氟烷同时阻断非 NMDA 和 NMDA受体介导的兴奋性突触后电流 (EPSC) 达到相似程度（IC50 值分别为 0.66 和 0.57 mM）。 3 通过降低细胞外钙浓度 ([Ca2+](o)) 而不是通过应用 CNQX (1 μM) 来部分阻断 EPSC，同时伴随着配对脉冲易化 (PPF) 的增加。氟烷诱导的 EPSC 阻断也与 PPF 增加相关。4 比较了氟烷对 α-氨基-3-羟基-5-甲基异恶唑-4-丙酸 (AMPA) 和激动剂离子电渗疗法诱导的 NMDA 受体介导电流的影响。 AMPA 诱导的电流被阻断，IC50 为 1.7 mM。 NMDA 诱导的电流对氟烷的敏感性显着降低（IC50 为 5.9 mM）。5 测试了氟烷对离子电渗疗法 AMPA 剂量反应曲线的影响。氟烷抑制对 AMPA 的最大反应，而不影响其 EC50，表明一种非竞争性抑制机制。6 氟烷的所有作用在终止药物暴露后都是可逆的。7 这些数据表明，氟烷通过突触前抑制谷氨酸释放和突触后阻断谷氨酸受体的 AMPA 亚型来阻断中枢谷氨酸能突触传递。
1 Whole-cell patch-clamp recordings in adult mouse hippocampal slices were used to test the mechanism by which the volatile anesthetic halothane inhibits glutamate receptor-mediated synaptic transmission. Non-N-methyl-D-aspartate (nonNMDA) and NMDA receptor-mediated currents in CA1 pyramidal cells were pharmacologically isolated by bath application of D,L-2-amino-5-phosphonovaleric acid (APV; 100 mu M) or 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX; 5 mu M), respectively.2 Halothane blocked both nonNMDA and NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) to a similar extent (IC50 values of 0.66 and 0.57 mM, respectively).3 Partial blockade of the EPSCs by lowering the extracellular concentration of calcium ([Ca2+](o)), but not by application of CNQX (1 mu M), was accompanied by an increase in paired-pulse facilitation (PPF). Halothane-induced blockade of the EPSCs also was associated with an increase in PPF.4 The effects of halothane on alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and NMDA receptor-mediated currents induced by agonist iontophoresis, were compared. AMPA-induced currents were blocked with an IC50 of 1.7 mM. NMDA-induced currents were significantly less sensitive to halothane (IC50 of 5.9 mM).5 The effect of halothane on iontophoretic AMPA dose-response curves was tested. Halothane suppressed the maximal response to AMPA without affecting its EC50, suggesting a noncompetitive mechanism of inhibition.6 All effects of halothane were reversible upon termination of the exposure to the drug.7 These data suggest that halothane blocks central glutamatergic synaptic transmission by presynaptically inhibiting glutamate release and postsynaptically blocking the AMPA subtype of glutamate receptors.