Gigout S, Louvel J, Kawasaki H, D'Antuono M, Armand V, Kurcewicz I, Olivier A, Laschet J, Turak B, Devaux B, Pumain R, Avoli M
INSERM U 573, Paris, 75014 France.
Neurobiol Dis. 2006 Jun;22(3):496-508. doi: 10.1016/j.nbd.2005.12.011. Epub 2006 Feb 14.
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 muM) 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.
从人类新皮质切片中获取场电位和细胞内记录，以研究缝隙连接（GJ）在神经网络同步中的作用。首先，我们研究了GJ阻滞剂（即羧苄青霉素、辛醇、奎宁和奎尼丁）对颞叶癫痫患者新皮质切片在应用4-氨基吡啶（4AP，50μM）和谷氨酸能受体拮抗剂期间产生的自发同步事件（持续时间 = 0.2 - 1.1秒；发生间隔 = 3 - 27秒）的影响。这些电位（在距离达5毫米处记录）的同步性在应用GJ阻滞剂后20分钟内降低，而高剂量的GJ阻滞剂延长治疗会使其在不同的时间进程中消失。其次，我们发现局灶性皮质发育异常（FCD）患者的切片在正常培养基中可产生自发同步放电（持续时间 = 0.4 - 8秒；发生间隔 = 0.5 - 90秒），这些放电（i）被NMDA受体拮抗剂消除，（ii）被羧苄青霉素减慢。最后，辛醇或羧苄青霉素阻断了FCD切片中4AP诱导的癫痫样放电（持续时间 = 长达35秒）。这些数据表明GJ在人类新皮质网络同步中起作用，并可能在FCD中促成癫痫样活动。
