Model-specific effects of bumetanide on epileptiform activity in the in-vitro intact hippocampus of the newborn mouse
Model-specific effects of bumetanide on epileptiform activity in the in-vitro intact hippocampus of the newborn mouse
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DOI：
10.1016/j.neuropharm.2007.06.015
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发表时间：
2007-09-01
影响因子：
4.7
通讯作者：
Luhmann, H. J.
中科院分区：
文献类型：
--
作者：
Kilb, W.;Sinning, A.;Luhmann, H. J.
不成熟的大脑更容易发生癫痫发作，而经典药物治疗通常对癫痫发作反应不佳。最近有人提出，布美他尼可以阻断 Na+ 依赖性 K+-Cl- 协同转运蛋白亚型 1 (NKCC1)，从而减弱 GABA 去极化反应，可以缓解未成熟神经系统中的癫痫样活动。为了评估布美他尼是否持续减弱癫痫样活动，我们使用出生后第 4-7 天完整小鼠海马制剂 CA3 区域的场电位记录，研究了 10 μM 布美他尼在五种不同的体外癫痫模型中的作用。布美他尼降低了 8.5 mM K+ 诱导的发作样事件 (ILE) 的幅度和频率，但增加了 1 μM 红藻氨酸诱导的 ILE 的频率。 10μM加巴嗪和30μM士的宁对配体门控Cl-通道的抑制诱导了发作间期活性(IA)，而布美他尼仅对这种活性产生轻微影响。细胞外 Mg2+ 的去除诱导 ILE 和 IA。布美他尼对这些 ILE 没有影响，但增强了 IA。含有 20 μM 4-AP 的低 Mg2+ 溶液诱导了晚期复发放电，布美他尼稍微减弱了这种放电。总之，我们的结果表明布美他尼在不同的体外癫痫模型中发挥不同的作用。 (C) 2007 Elsevier Ltd. 保留所有权利。
The immature brain has a higher susceptibility to develop seizures, which often respond poorly to classical pharmacological treatment. It has been recently suggested that bumetanide, which blocks Na+-dependent K+-Cl--cotransporter isoform 1 (NKCC1) and thus attenuates depolarizing GABAergic responses, could soothe epileptiform activity in immature nervous systems. To evaluate whether bumetanide consistently attenuates epileptiform activity, we investigated the effect of 10 mu M bumetanide in five different in-vitro epilepsy models using field potential recordings in the CA3 region of intact mouse hippocampal preparations at postnatal day 4-7. Bumetanide reduced amplitude and frequency of ictal-like events (ILE) induced by 8.5 mM K+, but it increased the frequency of ILE induced by 1 mu M kainate. Inhibition of ligand-gated Cl- channels by 10 mu M gabazine and 30 mu M strychnine induced interictal activity (IA) that was only marginally affected by bumetanide. Removal of extracellular Mg2+ induced both ILE and IA. Bumetanide had no effect on these ILE but enhanced the IA. Low-Mg2+ solution containing 20 mu M 4-AP induced late-recurrent discharges, which were slightly attenuated by bumetanide. In summary, our results demonstrate that bumetanide exerts diverse effects in different in-vitro epilepsy models. (C) 2007 Elsevier Ltd. All rights reserved.