Baraban S C, Schwartzkroin P A
Department of Neurological Surgery, University of Washington, Seattle 98195, USA.
Epilepsy Res. 1995 Oct;22(2):145-56. doi: 10.1016/0920-1211(95)00045-3.
Prenatal methylazoxymethanol acetate (MAMac) injection disrupts cell migration in developing rats. We investigated the electrophysiological characteristics of hippocampal CA1 pyramidal neurons from young MAMac-treated animals (postnatal days 25-35). In vitro intracellular recordings from CA1 cells in MAMac-treated tissue revealed resting membrane potential (mean, -61.5 +/- 1.5 mV), action potential amplitude (mean, 69 +/- 3.1 mV), action potential duration (mean, 2.1 +/- 0.2 ms), input resistance (mean, 51.5 +/- 3.6 M omega) and time constant (mean, 33.2 +/- 1.2 ms) similar to those of CA1 cells from control tissue. However, MAMac-treated tissue could be distinguished as having a higher percentage of cells (62% vs. 10%) which fire a burst of action potentials in response to suprathreshold current injection. The synaptic responses of CA1 cells in MAMac-treated and control tissue were comparable. The CA1 field response to stimulation was also comparable at all stimulus intensities tested (50-1500 microA). Elevation of extracellular potassium concentration ([K+]o) from 3 mM to 6 mM resulted in epileptiform discharge activity in response to stratum radiatum stimulation in all MAMac-treated slices (10/10) but in only one-third of controls (3/9). Spontaneous epileptiform discharges were also observed in the majority (8/13) of MAMac-treated slices bathed in 6 mM KCl but in no controls. These data suggest that MAMac treatment during fetal development not only disrupts normal anatomical organization but also leads to alterations in electrophysiological features of the hippocampal CA1 pyramidal cell region. As such, the MAMac model may provide insights into early onset seizure syndromes associated with developmental abnormalities.
产前注射乙酸甲基偶氮甲醇（MAMac）会扰乱发育中大鼠的细胞迁移。我们研究了来自幼年MAMac处理动物（出生后25 - 35天）海马CA1锥体神经元的电生理特性。对MAMac处理组织中的CA1细胞进行的体外细胞内记录显示，静息膜电位（平均值，-61.5 +/- 1.5 mV）、动作电位幅度（平均值，69 +/- 3.1 mV）、动作电位持续时间（平均值，2.1 +/- 0.2 ms）、输入电阻（平均值，51.5 +/- 3.6 MΩ）和时间常数（平均值，33.2 +/- 1.2 ms）与对照组织中的CA1细胞相似。然而，MAMac处理的组织可被区分出具有更高比例的细胞（62%对10%），这些细胞在响应阈上电流注入时会引发一阵动作电位。MAMac处理和对照组织中CA1细胞的突触反应相当。在所有测试的刺激强度（50 - 1500 μA）下，CA1场对刺激的反应也相当。将细胞外钾离子浓度（[K⁺]o）从3 mM升高到6 mM会导致所有MAMac处理切片（10/10）在响应辐射层刺激时出现癫痫样放电活动，但对照组中只有三分之一（3/9）出现。在浸泡于6 mM KCl的大多数MAMac处理切片（8/13）中也观察到自发癫痫样放电，但对照组中未观察到。这些数据表明，胎儿发育期间的MAMac处理不仅扰乱了正常的解剖组织结构，还导致海马CA1锥体细胞区域的电生理特征发生改变。因此，MAMac模型可能为与发育异常相关的早发性癫痫综合征提供见解。
