Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23508, USA.
Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23508, USA.
Bioelectrochemistry. 2021 Aug;140:107811. doi: 10.1016/j.bioelechem.2021.107811. Epub 2021 Apr 1.
Exposures to short-duration, strong electric field pulses have been utilized for stimulation, ablation, and the delivery of molecules into cells. Ultrashort, nanosecond duration pulses have shown unique benefits, but they require higher field strengths. One way to overcome this requirement is to use trains of nanosecond pulses with high repetition rates, up to the MHz range. Here we present a theoretical model to describe the effects of pulse trains on the plasma membrane and intracellular membranes modeled as resistively charged capacitors. We derive the induced membrane potential and the stimulation threshold as functions of pulse number, pulse duration, and repetition rate. This derivation provides a straightforward method to calculate the membrane charging time constant from experimental data. The derived excitation threshold agrees with nerve stimulation experiments, indicating that nanosecond pulses are not more effective than longer pulses in charging nerve fibers. The derived excitation threshold does not, however, correctly predict the nanosecond stimulation of cardiomyocytes. We show that a better agreement is possible if multiple charging time constants are considered. Finally, we expand the model to intracellular membranes and show that pulse trains do not lead to charge buildup, but can create significant oscillations of the intracellular membrane potential.
短时间、强电场脉冲的照射已被用于刺激、消融和分子递送入细胞。超短、纳秒持续时间的脉冲显示出了独特的优势，但它们需要更高的场强。克服这一要求的一种方法是使用具有高重复率的纳秒脉冲串，高达 MHz 范围。在这里，我们提出了一个理论模型来描述脉冲串对等离子膜和作为电阻性充电电容器建模的细胞内膜的影响。我们推导出了作为脉冲数、脉冲持续时间和重复率函数的诱导膜电位和刺激阈值。这种推导为从实验数据计算膜充电时间常数提供了一种直接的方法。推导出的激发阈值与神经刺激实验一致，表明纳秒脉冲在给神经纤维充电方面并不比长脉冲更有效。然而，推导出的激发阈值并不能正确预测纳秒刺激心肌细胞的情况。我们表明，如果考虑多个充电时间常数，则可以得到更好的一致性。最后，我们将模型扩展到细胞内膜，并表明脉冲串不会导致电荷积累，但可以在细胞内膜电位上产生显著的振荡。
