Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA, 23508, USA.
Department of Electrical and Computer Engineering, Old Dominion University, Norfolk, VA, 23508, USA.
Sci Rep. 2017 Sep 5;7(1):10453. doi: 10.1038/s41598-017-10282-5.
Modern technologies enable deep tissue focusing of nanosecond pulsed electric field (nsPEF) for non-invasive nerve and muscle stimulation. However, it is not known if PEF orders of magnitude shorter than the activation time of voltage-gated sodium channels (VGSC) would evoke action potentials (APs). One plausible scenario requires the loss of membrane integrity (electroporation) and resulting depolarization as an intermediate step. We report, for the first time, that the excitation of a peripheral nerve can be accomplished by 12-ns PEF without electroporation. 12-ns stimuli at 4.1-11 kV (3.3-8.8 kV/cm) evoked APs similarly to conventional stimuli (100-250 μs, 1-5 V, 103-515 V/m), except for having higher selectivity for the faster nerve fibers. Nerves sustained repeated tetanic stimulations (50 Hz or 100 Hz for 1 min) alternately by 12-ns PEF and by conventional pulses. Such tetani caused a modest AP decrease, to a similar extent for both types of stimuli. Nerve refractory properties were not affected. The lack of cumulative damages even from tens of thousands of 12-ns stimuli and the similarities with the conventional stimulation prove VGSC activation by nsPEF without nerve membrane damage.
现代技术使纳秒脉冲电场（nsPEF）能够实现深层组织聚焦，从而实现非侵入性的神经和肌肉刺激。然而，目前尚不清楚是否存在比电压门控钠离子通道（VGSC）激活时间更短的 PEF 能够引发动作电位（AP）。一种合理的情况是需要膜完整性丧失（电穿孔）和随之而来的去极化作为中间步骤。我们首次报告，12-ns 的 PEF 无需电穿孔即可激发外周神经。4.1-11 kV（3.3-8.8 kV/cm）的 12-ns 刺激与传统刺激（100-250 μs、1-5 V、103-515 V/m）一样能引发 AP，除了对更快的神经纤维具有更高的选择性。神经可以通过 12-ns 的 PEF 和传统脉冲交替进行重复的强直刺激（50 Hz 或 100 Hz，持续 1 分钟）。这种强直刺激导致 AP 适度下降，两种刺激类型的下降程度相似。神经不应性特性不受影响。即使受到数万次 12-ns 刺激的累积损伤也很小，并且与传统刺激的相似性证明了 VGSC 可以通过 nsPEF 激活而不会导致神经膜损伤。
