产前应激对子代大鼠海马CA3区神经元Ca2+和K+通道的影响

本研究的目的在于探讨产前应激对子代大鼠海马CA3神经元高电压激活(HVA)钙通道、延迟整流钾电流(delayedrectifierpotassiumcurrents,IKD)的影响。产前应激(prenatalstress,PNS)组孕鼠孕晚期给予束缚应激,应用全细胞膜片钳技术进行研究。结果显示产前应激增加了子代海马CA3神经元HVA钙通道峰电流幅值,对照组和产前应激组子代CA3神经元平均最大HVA钙电流峰值分别为-576.52±7.03pA和-702.05±6.82pA(P<0.01)。同时未改变其电导-电压关系,也未改变延迟整流钾通道电流-电压关系、电导-电压关系。结果提示,在胎儿发育的关键时期,给予母体产前应激,引起子代海马神经元HVA钙电流增加,其机制一方面PNS导致皮质酮升高,从而可能增加HVA钙通道mRNA表达;另一方面PNS所致反应性氧化产物(reactiveoxygenspecies,ROS)增多,后者可能通过磷酸化HVACa2 通道亚单位,从而提高HVA钙电流幅值。

THE EFFECTS OF PRENATAL STRESS ON Ca2+ CHANNEL AND K+ CHANNEL OF HIPPOCAMPAL CA3 PYRAMIDAL NEURONS IN RAT OFFSPRING

To investigate the effects of prenatal stress (PNS) on high-voltage-activated (HVA) Ca2+ channel and delayed rectifier potassium currents (I(KD)) of freshly isolated rat offspring hippocampal CA3 pyramidal neurons, the pregnant rats of PNS group were exposed to restraint stress and patch clamp technique of whole-cell mode was employed to record HVA Ca2+ and K+ channel currents in hippocampal CA3 pyramidal neurons. It was observed that PNS increased HVA calcium peak current amplitude. The maximal HVA calcium peak current amplitudes were -576.52 +/- 7.03 pA in the control group and -702.05 +/- 6.82 pA in the PNS group respectively (P < 0.01). The conductance-voltage relationship of HVA Ca2+ channel was not changed. Current-voltage relationship and conductance-voltage relationship of I(KD) in offspring CA3 neurons were also not affected by PNS. The data suggested that exposure of pregnant animals to a period of stress could impose lasting effects on the offspring hippocampus CA3 neurons Ca2+ channel during a critical phase of fetal development. The mechanism may include two ways. One was that high CORT led to enhance level of expression for the HVA Ca2+ channel subunit mRNAs and increased HVA calcium currents. Another was that PNS caused an increase in the production of ROS in hippocampal CA3 region and ROS caused an increase in the phosphorylation of HVA Ca2+ channel of offspring hippocampal CA3 neurons.