Frank Reidy Research Center for Bioelectrics, Old Dominion University, 4211 Monarch Way, Suite 300, Norfolk, VA, 23508, USA.
Department of Electrical and Computer Engineering, Old Dominion University, Norfolk, VA, USA.
Cell Mol Life Sci. 2019 Nov;76(22):4539-4550. doi: 10.1007/s00018-019-03126-0. Epub 2019 May 4.
The initiation of action potentials (APs) by membrane depolarization occurs after a brief vulnerability period, during which excitation can be abolished by the reversal of the stimulus polarity. This vulnerability period is determined by the time needed for gating of voltage-gated sodium channels (VGSC). We compared nerve excitation by ultra-short uni- and bipolar stimuli to define the time frame of bipolar cancellation and of AP initiation. Propagating APs in isolated frog sciatic nerve were elicited by cathodic pulses (200 ns-300 µs), followed by an anodic (canceling) pulse of the same duration after a 0-200-µs delay. We found that the earliest and the latest boundaries for opening the critical number of VGSC needed to initiate AP are, respectively, between 11 and 20 µs and between 100 and 200 µs after the onset of depolarization. Stronger depolarization accelerated AP initiation, apparently due to faster VGSC opening, but not beyond the 11-µs limit. Bipolar cancellation was augmented by reducing pulse duration, shortening the delay between pulses, decreasing the amplitude of the cathodic pulse, and increasing the amplitude of the anodic one. Some of these characteristics contrasted the bipolar cancellation of cell membrane electroporation (Pakhomov et al. in Bioelectrochemistry 122:123-133, 2018; Gianulis et al. in Bioelectrochemistry 119:10-19, 2017), suggesting different mechanisms. The ratio of nerve excitation thresholds for a unipolar cathodic pulse and a symmetrical bipolar pulse increased as a power function as the pulse duration decreased, in remarkable agreement with the predictions of SENN model of nerve excitation (Reilly and Diamant in Health Phys 83(3):356-365, 2002).
动作电位（APs）的产生是由膜去极化引起的，发生在短暂的易损期之后，在此期间，通过反转刺激极性可以消除兴奋。这个易损期由电压门控钠离子通道（VGSC）的门控时间决定。我们比较了超短单极和双极刺激对神经的兴奋作用，以确定双极消除和 AP 起始的时间框架。通过阴极脉冲（200ns-300µs）在分离的青蛙坐骨神经中引发传播的 APs，然后在 0-200µs 的延迟后，用相同持续时间的阳极（取消）脉冲跟随。我们发现，开启启动 AP 所需的临界数量 VGSC 的最早和最晚边界分别在去极化开始后 11-20µs 和 100-200µs 之间。更强的去极化加速了 AP 的起始，显然是由于 VGSC 更快地打开，但不能超过 11µs 的限制。通过减少脉冲持续时间、缩短脉冲之间的延迟、减小阴极脉冲的幅度以及增大阳极脉冲的幅度，可以增强双极消除。其中一些特性与细胞膜电穿孔的双极消除（Pakhomov 等人，Bioelectrochemistry 122:123-133, 2018；Gianulis 等人，Bioelectrochemistry 119:10-19, 2017）相反，表明存在不同的机制。单极阴极脉冲和对称双极脉冲的神经兴奋阈值之比随着脉冲持续时间的减少而呈幂函数增加，与神经兴奋 SENN 模型的预测（Reilly 和 Diamant，Health Phys 83(3):356-365, 2002）非常吻合。
