Dual actions of volatile anesthetics on GABAA IPSCs -: Dissociation of blocking and prolonging effects
Dual actions of volatile anesthetics on GABAA IPSCs -: Dissociation of blocking and prolonging effects
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DOI：
10.1097/00000542-199901000-00018
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发表时间：
1999-01-01
期刊：
影响因子：
8.8
通讯作者：
Pearce, RA
中科院分区：
文献类型：
--
作者：
Banks, MI;Pearce, RA
背景：挥发性药物在临床相关浓度下改变抑制性突触后电流（IPSCs），这一作用被认为对其行为效应有重要贡献。作者通过评估安氟烷、异氟烷和氟烷对大鼠海马切片诱导多能干细胞调节的浓度依赖性来研究这些作用的机制。方法：从CAI锥体神经元中记录动作电位不依赖性γ -氨基丁酸、微型IPSCs [mIPSCs]。利用对mIPSC振幅的影响来区分挥发性药物的突触前（改变释放）和突触后（改变受体反应）作用。比较了各挥发剂阻断和延长作用的浓度依赖性，以确定单一调节过程是否可以解释这两种作用。结果：挥发性麻醉剂的使用延长了mIPSCs的衰减时间，并呈剂量依赖性地降低了其振幅。对异氟烷和安氟烷衰变时间的影响无法区分。在所有浓度下，安氟醚的阻断作用均显著大于异氟醚。尽管有阻断作用，但这些药物的净作用是增强的抑制作用，因为电荷转移总是明显大于对照组。异氟醚，以及较小程度上的安氟醚和氟烷，造成了对微毒素敏感的基线噪声增加。所有药物的mIPSC频率也有中度增加。结论：这些结果表明，安氟醚、异氟醚和氟烷通过直接的突触后作用降低IPSC振幅。此外，药物作用的浓度依赖性揭示了对IPSCs振幅和时间过程的影响之间的分离，表明这两种作用背后的不同机制。
Background: Volatile agents alter inhibitory postsynaptic currents (IPSCs) at clinically relevant concentrations, an action that is thought to make an important contribution to their behavioral effects. The authors investigated the mechanisms underlying these effects by evaluating the concentration dependence of modulation by enflurane, isoflurane, and halothane of IPSCs in rat hippocampal slices.Methods: Action potential-independent gamma-aminobutyric acid, IPSCs (miniature IPSCs [mIPSCs]) were recorded from CAI pyramidal neurons. The effects on mIPSC amplitude were used to distinguish between presynaptic (altered release) and postsynaptic (altered receptor response) actions of volatile agents. The concentration dependence of blocking and prolonging actions was compared among the volatile agents to determine whether a single modulatory process could account for both effects.Results: The application of volatile anesthetics prolonged the decay and reduced the amplitude of mIPSCs in a dose-dependent manner. The effects on decay time for isoflurane and enflurane could not be distinguished. Non ever, the blocking effect of enflurane was significantly greater than that of isoflurane at all concentrations. Despite the blocking effect, the net action of these agents was enhanced inhibition, because charge transfer was always significantly greater than control. Isoflurane, and to a lesser extent enflurane and halothane, caused a picrotoxin-sensitive increase in baseline noise. Moderate increases in mIPSC frequency were also observed for all agents.Conclusions: These results show that enflurane, isoflurane, and halothane reduce IPSC amplitude through a direct postsynaptic action. Furthermore, the concentration dependence of the actions of the agents reveals a dissociation between the effects on the amplitude and the time course of IPSCs, suggesting that distinct mechanisms underlie the two actions.