Effects of gap junction blockers on human neocortical synchronization
Effects of gap junction blockers on human neocortical synchronization
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DOI：
10.1016/j.nbd.2005.12.011
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发表时间：
2006-06-01
影响因子：
6.1
通讯作者：
Avoli, M.
中科院分区：
文献类型：
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作者：
Gigout, S.;Louvel, J.;Avoli, M.
为了研究缝隙连接(GJ)在神经元网络同步化中的作用，从人的新皮质脑片获得了场电位和细胞内记录。首先，我们观察了GJ阻滞剂(即甘草酮、辛醇、奎宁和奎尼丁)对应用4-氨基吡啶(4AP，50mM)和谷氨酸受体拮抗剂时，由癫痫患者大脑皮质脑片产生的自发同步事件(持续时间为0.2~1.1 S，发作间隔为3~2 7个S)的影响。GJ受体阻滞剂在用药后20min内可降低这些电位的同步性，而较高剂量的长时间GJ受体阻滞剂可使这些电位的同步性随时间变化而消失。其次，我们发现局灶性皮质发育不良患者脑片在正常介质中可产生自发同步放电(持续时间为0.4~8个S，出现间隔为0.5~90个S)，且(1)被N-甲基-D-天冬氨酸受体拮抗剂阻断，(2)被甘草次酸减慢。最后，辛醇或甘草酮阻断4AP诱发的FCD脑片的发作性样放电(持续时间=35 S)。这些数据表明，GJ在人类新皮质网络的同步化中起作用，并可能在FCD中实现癫痫样活动。(C)2006 Elsevier Inc.保留所有权利。
Field potentials and intracellular recordings were obtained from human neocortical slices to study the role of gap junctions (GJ) in neuronal network synchronization. First, we examined the effects of GJ blockers (i.e., carbenoxolone, octanol, quinine, and quinidine) on the spontaneous synchronous events (duration = 0.2-1.1 s; intervals of occurrence = 3-27 s) generated by neocortical slices obtained from temporal lobe epileptic patients during application of 4-aminopyridine (4AP, 50 mu M) and glutamatergic receptor antagonists. The synchronicity of these potentials (recorded at distances up to 5 mm) was decreased by GJ blockers within 20 min of application, while prolonged GJ blockers treatment at higher doses made them disappear with different time courses. Second, we found that slices from patients with focal cortical dysplasia (FCD) could generate in normal medium spontaneous synchronous discharges (duration = 0.4-8 s; intervals of occurrence = 0.5-90 s) that were (I) abolished by NMDA receptor antagonists and (ii) slowed down by carbenoxolone. Finally, octanol or carbenoxolone blocked 4AP-induced ictal-like discharges (duration = up to 35 s) in FCD slices. These data indicate that GJ play a role in synchronizing human neocortical networks and may implement epileptiform activity in FCD. (c) 2006 Elsevier Inc. All rights reserved.