Seizure-like activity in the disinhibited CA1 minislice of adult guinea-pigs
Seizure-like activity in the disinhibited CA1 minislice of adult guinea-pigs
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DOI：
10.1111/j.1469-7793.2001.0713e.x
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发表时间：
2001-05-01
影响因子：
5.5
通讯作者：
Stelzer, A
中科院分区：
文献类型：
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作者：
Karnup, S;Stelzer, A
1.在药物阻断CA1区(CA3区)GABA(A)受体功能的过程中监测自发活动。突触抑制可被竞争性GABA(A)拮抗剂荷包牡丹碱(Bic)或GABAZINE(GBZ)和氯离子通道阻滞剂印防己毒素(PTX)阻断。采用锐尖电极在放射层和锥体层进行细胞外和细胞内记录。在低浓度的拮抗剂(Bic，GBZ：1-10um；Ptx：<；100M)下，出现如前所述的同步爆发(持续时间为500ms，发作间期活动)。然而，在高浓度(Bic，GBZ：50-100M；PTX：100-200um)存在下，在88个脑片中有67个观察到癫痫样发作事件(持续时间4-17个S)。没有采用其他增加兴奋性的实验措施：阳离子浓度([Ca~(2+)](O)=2 mm，[Mg~(2+)](O)=1.7 mm，[K+](O)=3 mm)和记录温度(30-32℃)是标准的，GABA(B)介导的抑制是完整的。在全层记录中，发作间期活动突出，但发作事件较少。当传入刺激引起发作间歇性反应时，发作活动也减少。兴奋性传递的拮抗剂CNQX(40um)或D-AP5(50um)可逆地阻断发作活动。去抑制诱导的癫痫发作不依赖于I组mGluR的激活，因为在I组mGluR拮抗剂(AIDB或4CPG)的存在下，它不能被阻止。(RS)-3，5-DHPG通过I组mGluR非依赖机制阻止发作事件的诱导并逆转发作事件的第三成分。
1. Spontaneous activity was monitored during pharmacological blockade of GABA(A) receptor function in the CA1 minislice (CA3 was cut off). Synaptic inhibition was blocked by competitive GABA(A) antagonists bicuculline-methiodide (Bic) or GABAZINE (GBZ) and the chloride channel blocker picrotoxin (PTX). Extra- and intracellular recordings using sharp electrodes were carried out in stratum radiatum and pyramidale.2. At low antagonist concentrations (Bic, GBZ: 1-10 muM; PTX: < 100 M), synchronized bursts (< 500 ms in duration, interictal activity) were seen as described previously. However, in the presence of high concentrations (Bic, GBZ: 50-100 M; PTX: 100-200 muM), seizure-like, ictal events (duration 4-17 s) ware observed in 67 of 88 slices. No other experimental measures to increase excitability were applied: cation concentrations ([Ca2+](o) = 2 mM, [Mg2+](o) = 1.7 mM, [K+](o) = 3 mM) and recording temperature (30-32 degreesC) were standard and GABA(B)-mediated inhibition was intact.3. In whole-slice recordings prominent interictal activity, but fewer ictal events were observed. A reduced ictal activity was also observed when interictal-like responses were evoked by afferent stimulation.4. Ictal activity was reversibly blocked by antagonists of excitatory transmission, CNQX (40 muM) or D-AP5 (50 muM).5. Disinhibition-induced ictal development did not rely on group I mGluR activation as it was not prevented in the presence of group I mGluR antagonists (AIDB or 4CPG).6. (RS)-3,5-DHPG prevented the induction and reversed the tertiary component of the ictal event through a group I mGluR-independent mechanism.