细胞内外膜跨膜电位频率响应的仿真研究

为研究ns脉冲电场诱导细胞跨膜电位改变的效应,在提出一种球形单细胞内外膜跨膜电位频率响应模型后给出了细胞内外膜跨膜电位的仿真计算方法。通过对频率响应的仿真分析,发现外膜跨膜电位表现出一阶低通滤波器特性,而内膜跨膜电位表现出一阶带通滤波器特性。在内膜频率响应中心频率到上限截止频率的范围内,内膜跨膜电位大于外膜,同时能保持在较高水平,这将有利于诱导细胞内电处理效应。计算结果与实验结果相吻合,为ns脉冲电场治疗肿瘤的窗口参数合理选择提供了一定的理论依据。

Study of Frequency Response of Transmembrane Potential on Cellular Inner and Outer Membrane

This paper presented a novel field model for singular physiological cell which can be used to analyze the frequency response of the transmembrane potential on cellular inner and outer membrane.Based on the model,the simulation method of the frequency response of the transmembrane potential on cellular inner and outer membrane was proposed according to the electromagnetic theory.From the simulation and analysis of the frequency response,it can be found that the frequency response of the transmembrane potential on cellular outer membrane shows the first-order low-pass filter characteristic,while that on inner membrane can be treated as a first-order band-pass filter.The transmembrane potential on inner membrane not only keeps a higher value,but also exceeds that on outer membrane in the range from center to upper cut-off frequency of the frequency response of the transmembrane potential on inner membrane.This property is in favor of applying nanosecond pulsed electric field(nsPEF) to induce intracellular electromanipulation(IEM).After cells labeled with Rhodamine 123 were exposed to nanosecond pulses with durations of 130ns,250ns and 600ns,respectively,the fluorescence intensity indicating the transmembrane potential on mitochondrial membrane was measured under confocal laser scanning microscope (CLSM).As a result,the cells treated with 250ns-PEF demonstrate a higher transmembrane potential on mitochondrial membrane than the other groups.The experimental evidence agrees well with the simulation result.Therefore,the simulation result provides a theoretical guidance to choosing reasonable window parameters for application of nanosecond pulse to tumor treatment.