COX-2抑制剂对幼鼠海马CA1区锥体神经元钠通道的影响

The effects of COX-2 inhibitor on voltage-dependent sodium channel in hippocampal CA1 pyramidal neuron in immature rats

目的：研究环氧合酶-2（cyclooxygenase-2，COX-2）抑制剂硝基苯一甲磺酸（NS398）对大鼠海马CAl区锥体神经元电压依赖性钠通道的影响，以及在幼鼠痫性发作中的作用。方法：出生后14d龄SD大鼠制作海马组织脑切片，脑片灌流液中灌流不同浓度NS-398，全细胞记录在阶跃模式（episod—ic）中，通过相应的刺激方案（protocol），记录对电压依赖性钠通道电流密度及幅度的影响，观察对钠通道激活及失活曲线的影响。结果：①加入20μMol／L（μM）NS-398能明显抑制电流密度，而且在最大激活电位时抑制最明显（P〈O．01），抑制呈电压依赖性，但是不能改变其最大激活电位；②加入20μmol／LNS-398不能明显改变钠通道的电压依赖性激活状态（P〉0．05）；③加入20Fmol／LNS-398，电压依赖性钠失活电流的失活曲线明显向负极化方向移动（左移5．2mV，P〈0．05）；④相同指令电压的刺激下，加入NS-398组的1／Lmax比正常组减小，NS-398能明显延长电压依赖性钠电流的失活时间。结论：COX-2抑制剂能抑制大鼠海马脑片CAl区锥体神经元电压依赖性钠通道，延长电压依赖性钠电流的失活时间；减少Na＋电流，延缓动作电位的发放和传播，降低神经元的兴奋性。

Objective：To study the mechanism of COX-2 inhibitor in immature epileptic ratsby ob- serving the effects of COX-2 inhibitor on hippocampal pyramidal neuron in vitro hippocampal tissue epi- leptiform discharges and the alterations of synaptie activities. Methods.. Hippocampal slices were prepared from 2wk-old rats with for Sprague-Dawley （SD）whole-cell patch clamp recording. The hippocampal slice epileptic models were induced by dabbling penicillin into the slices. The alterations of the CA1 py- ramidal neurons electrophysiologica[ properties in epileptic rats after dabbling different concentration of COX-2 inhibitor （NS-398） into the slices were analyzed with whole cell recording technology. Results.. In the brain slices of penicillin-induced epileptic discharges Meanwhile NS -398 significantly enhanced the frequency and prolonged the decayed time of SLPSCs, but little impact on the current rate. Concluslon： The impact of NS-398 occurred in the voltage-dependent sodium current： NS -398 can reduce the current rate and extent the no-answer period of the voltage-dependent sodium channel to decreaseg the open frequency of sodium channel by extending inactivation recovery phase from deactivation,and neuronal action potential frequency of issuance corresponding declined;