The effect of propofol on CA1 pyramidal cell excitability and GABA(A)-mediated inhibition in the rat hippocampal slice
The effect of propofol on CA1 pyramidal cell excitability and GABA(A)-mediated inhibition in the rat hippocampal slice
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DOI：
10.1016/0024-3205(96)00243-3
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发表时间：
1996-05-24
期刊：
影响因子：
6.1
通讯作者：
Joy, RM
中科院分区：
文献类型：
--
作者：
Albertson, TE;Walby, WF;Joy, RM
采用体外配对脉冲顺向刺激技术检测异丙酚对大鼠海马切片兴奋性传入末梢、CA1 锥体细胞和复发性侧支诱发抑制的影响。 400μm厚的海马切片灌注含氧人工脑脊液，并将电极放置在CAI区域以记录细胞外场群体尖峰（PS）或兴奋性突触后电位（EPSP）对刺激Schaffer侧支/连合纤维的反应。使用配对脉冲技术测量γ-氨基丁酸（GABA）介导的反复抑制。丙泊酚 (7-28 μM) 的主要作用是 GABA 介导的抑制的强度和持续时间呈剂量和时间依赖性增加。通过接触已知的 GABA(A) 拮抗剂，包括印防己毒素、荷包牡丹碱和戊四唑，可以快速、完全逆转丙泊酚的这种作用。氯离子通道拮抗剂 4,4'-二异硫氰芪-2,2'-二磺酸 (DIDS) 也可以逆转这种情况。它不被中枢（氟马西尼）或外周（PK11195）苯二氮卓类拮抗剂拮抗。拮抗剂印防己毒素和戊四唑也可逆转内源性抑制。使用刺激异丙酚构建的输入/输出曲线在较高刺激强度下仅引起 EPSP 的小幅增强，但对 PS 幅度没有影响。这些研究与异丙酚具有 GABA(A)-氯通道机制导致其对大鼠海马切片中的复发性侧支诱发抑制的影响一致。
An in vitro paired-pulse orthodromic stimulation technique was used to examine the effects of propofol on excitatory afferent terminals, CA1 pyramidal cells and recurrent collateral evoked inhibition in the rat hippocampal slice. Hippocampal slices 400 mu m thick were perfused with oxygenated artificial cerebrospinal fluid, and electrodes were placed in the CAI region to record extracellular field population spike (PS) or excitatory postsynaptic potential (EPSP) responses to stimulation of Schaffer collateral/commissural fibers. Gamma-aminobutyric acid (GABA)-mediated recurrent inhibition was measured using a paired-pulse technique. The major effect of propofol (7-28 mu M) was a dose and time dependent increase in the intensity and duration of GABA-mediated inhibition. This propofol effect could be rapidly and completely reversed by exposure to known GABA(A) antagonists, including picrotoxin, bicuculline and pentylenetetrazol. It was also reversed by the chloride channel antagonist, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). It was not antagonized by central (flumazenil) or peripheral (PK11195) benzodiazepine antagonists. Reversal of endogenous inhibition was also noted with the antagonists picrotoxin and pentylenetetrazol. Input/output curves constructed using stimulus propofol caused only a small enhancement of EPSPs at higher stimulus intensities but had no effect on PS amplitudes. These studies are consistent with propofol having a GABA(A)-chloride channel mechanism causing its effect on recurrent collateral evoked inhibition in the rat hippocampal slice.