Neonatal Propofol and Etomidate Exposure Enhance Inhibitory Synaptic Transmission in Hippocampal Cornus Ammonis 1 Pyramidal Neurons.
Neonatal Propofol and Etomidate Exposure Enhance Inhibitory Synaptic Transmission in Hippocampal Cornus Ammonis 1 Pyramidal Neurons.
复制标题
DOI：
10.4103/0366-6999.193459
复制
发表时间：
2016-11-20
影响因子：
6.1
通讯作者：
Xu CQ
中科院分区：
文献类型：
--
作者：
Zhang JQ;Xu WY;Xu CQ
丙泊酚和依托咪酯是目前临床使用的最重要的静脉全身麻醉剂，可介导γ-氨基丁酸（GABAergic）突触传递。然而，它们对新生儿丙泊酚或依托咪酯暴露诱导的 GABA 能突触传递的长期影响仍不清楚。我们研究了新生儿丙泊酚和依托咪酯给药后长期 GABA 能神经传递的改变。 Sprague-Dawley 幼鼠在出生后 4-6 天接受 6 小时异丙酚诱导麻醉或 5 小时依托咪酯诱导麻醉。我们对出生后 80-90 天的急性海马切片的 Cornus ammonis 1 区域的锥体细胞进行了全细胞膜片钳记录。测量了自发和微型抑制性 GABA 电流（自发抑制性突触后电流 [sIPSCs] 和微型抑制性突触后电流 [mIPSCs]）及其动力学特征。还检查了谷氨酸能对抑制传播的补强作用以及布美他尼对新生儿丙泊酚暴露的影响。新生儿异丙酚暴露显着增加了mIPSCs的频率（从1.87±0.35 Hz到3.43±0.51 Hz，P<0.05），并且不影响mIPSCs和sIPSCs的幅度。丙泊酚和依托咪酯均减慢了 mIPSC 动力学的衰减时间（168.39 ± 27.91 ms 和 267.02 ± 100.08 ms vs. 68.18 ± 12.43 ms；P < 0.05）。布美他尼显着阻止频率增加并逆转新生儿异丙酚暴露引起的 mIPSC 动力学改变（3.01 ± 0.45 Hz 和 94.30 ± 32.56 ms）。新生儿异丙酚和依托咪酯暴露对抑制 GABA 能传播具有长期影响。异丙酚可能作用于 GABA 能突触内的突触前和突触后 GABA 受体 A (GABAA) 受体，并损害 GABA 能突触的谷氨酸强直输入；依托咪酯可能作用于突触后部位。
Propofol and etomidate are the most important intravenous general anesthetics in the current clinical use and that mediate gamma-aminobutyric acid's (GABAergic) synaptic transmission. However, their long-term effects on GABAergic synaptic transmission induced by neonatal propofol or etomidate exposure remain unclear. We investigated the long-term GABAergic neurotransmission alterations, following neonatal propofol and etomidate administration. Sprague-Dawley rat pups at postnatal days 4–6 were underwent 6-h-long propofol-induced or 5-h-long etomidate-induced anesthesia. We performed whole-cell patch-clamp recording from pyramidal cells in the cornus ammonis 1 area of acute hippocampal slices of postnatal 80–90 days. Spontaneous and miniature inhibitory GABAergic currents (spontaneous inhibitory postsynaptic currents [sIPSCs] and miniature inhibitory postsynaptic currents [mIPSCs]) and their kinetic characters were measured. The glutamatergic tonic effect on inhibitory transmission and the effect of bumetanide on neonatal propofol exposure were also examined. Neonatal propofol exposure significantly increased the frequency of mIPSCs (from 1.87 ± 0.35 Hz to 3.43 ± 0.51 Hz, P < 0.05) and did not affect the amplitude of mIPSCs and sIPSCs. Both propofol and etomidate slowed the decay time of mIPSCs kinetics (168.39 ± 27.91 ms and 267.02 ± 100.08 ms vs. 68.18 ± 12.43 ms; P < 0.05). Bumetanide significantly blocked the frequency increase and reversed the kinetic alteration of mIPSCs induced by neonatal propofol exposure (3.01 ± 0.45 Hz and 94.30 ± 32.56 ms). Neonatal propofol and etomidate exposure has long-term effects on inhibitory GABAergic transmission. Propofol might act at pre- and post-synaptic GABA receptor A (GABAA) receptors within GABAergic synapses and impairs the glutamatergic tonic input to GABAergic synapses; etomidate might act at the postsynaptic site.