伽玛刀对大鼠皮层神经元钠电流的影响

Effects of gamma knife irradiation on voltage-dependent sodium current of rat cortical neurons

目的观察伽玛刀对体外培养大鼠皮层神经元电压依赖性钠电流的影响。方法将原代培养的神经元随机分为实验组和对照组，通过立体定向技术和18mm准直器对实验组原代培养大鼠皮层神经元实施伽玛刀照射，中心剂量30Gy。伽玛刀照射后1、3、7、10d通过膜片钳技术在全细胞模式下记录实验组和对照组皮层神经元的电压依赖性钠电流，每组每时间点记录6～8个神经元。结果实验组皮层神经元在伽玛刀照射后1、3、7、10d时的电压依赖性钠电流峰值密度（pA／pF）分别为（89．94±4．65）、（84．13±4．56）、（80．27±5．18）和（80．80±5．41），与对照组神经元电压依赖性钠电流峰值密度[照射后1、3、7、10d分别为（100．93±4．63）、（97．89±4．77）、（100．76±5．90）和（102．84±4．08）]相比，均显著减小（P〈0．05），且减小程度随观察时间延长而增加，呈一定时间依赖性。另外，实验组神经元电压依赖性钠电流的I—V曲线明显上移，下降支明显右移。结论伽玛刀照射通过抑制电压依赖性钠离子通道的功能引起大鼠皮层神经元兴奋性下降，可能是伽玛刀照射抑制癫痫发作的分子机制之一。

Objective To investigate the effects of Gamma knife surgery （GKS） on voltage-dependent sodium current of primarily cultured rat cortical neurons in vitro. Methods Primarily cultured neurons were randomly divided into experimental and control groups. Using stereotactic technique and 18 mm collimating device, we performed gamma knife irradiation on primarily cultured cortical neurons with a maximum dose of 30Gy. After irradiation, the neurons of experimental and control groups were cultured for additonal 1, 3, 7 and 10 d respectively of each group, 6 - 8 neurons were examined at one time point. Results The voltage-dependent sodium current peak densities （pA/pF） of primarily cultured cortical neurons of experimental groups recorded at 1, 3, 7 and 10 d after gamma knife irradiation were 89.94±4. 65, 84. 13±4. 56, 80. 27±5. 18 and 80. 80±5. 41, respectively. Compared with control groups （current peak densities at 1, 3, 7 and 10 d were 100. 93±4. 63,97.89±4. 77,100. 76±5.90 and 102. 84±4. 08, respectively）, were significantly reduced by GKS in a time-dependent manner （P 〈0. 05）. The I-V curves of voltage-dependent sodium current of experimental groups were also upwardly shifted significantly, while the decents of I-V curves shifted to the right. Conclusions Gamma knife irradiation reduced the excitability of primarily cultured rat cortical neurons through inhibiting the ability of voltage-dependent sodium channels, which might represent a possible mechanism underlying the therapeutic effects of gamma knife irradiation on epileptic seizure.