Herzog R I, Cummins T R, Waxman S G
Department of Neurology, Paralyzed Veterans of America/Eastern Paralyzed Veterans Association Neuroscience Research Center, Yale School of Medicine, New Haven, CT 06510, USA.
J Neurophysiol. 2001 Sep;86(3):1351-64. doi: 10.1152/jn.2001.86.3.1351.
Small dorsal root ganglion (DRG) neurons, which include nociceptors, express multiple voltage-gated sodium currents. In addition to a classical fast inactivating tetrodotoxin-sensitive (TTX-S) sodium current, many of these cells express a TTX-resistant (TTX-R) sodium current that activates near -70 mV and is persistent at negative potentials. To investigate the possible contributions of this TTX-R persistent (TTX-RP) current to neuronal excitability, we carried out computer simulations using the Neuron program with TTX-S and -RP currents, fit by the Hodgkin-Huxley model, that closely matched the currents recorded from small DRG neurons. In contrast to fast TTX-S current, which was well fit using a m(3)h model, the persistent TTX-R current was not well fit by an m(3)h model and was better fit using an mh model. The persistent TTX-R current had a strong influence on resting potential, shifting it from -70 to -49.1 mV. Inclusion of an ultra-slow inactivation gate in the persistent current model reduced the potential shift only slightly, to -56.6 mV. The persistent TTX-R current also enhanced the response to depolarizing inputs that were subthreshold for spike electrogenesis. In addition, the presence of persistent TTX-R current predisposed the cell to anode break excitation. These results suggest that, while the persistent TTX-R current is not a major contributor to the rapid depolarizing phase of the action potential, it contributes to setting the electrogenic properties of small DRG neurons by modulating their resting potentials and response to subthreshold stimuli.
小背根神经节（DRG）神经元，其中包括伤害感受器，表达多种电压门控钠电流。除了经典的快速失活河豚毒素敏感（TTX - S）钠电流外，这些细胞中的许多还表达一种河豚毒素抗性（TTX - R）钠电流，该电流在接近 -70 mV时激活，并在负电位时持续存在。为了研究这种TTX - R持续电流（TTX - RP）对神经元兴奋性的可能贡献，我们使用Neuron程序对TTX - S和 - RP电流进行了计算机模拟，这些电流由霍奇金 - 赫胥黎模型拟合，与从小DRG神经元记录的电流紧密匹配。与使用m(3)h模型能很好拟合的快速TTX - S电流不同，持续的TTX - R电流不能被m(3)h模型很好地拟合，而使用mh模型拟合效果更好。持续的TTX - R电流对静息电位有强烈影响，使其从 -70 mV变为 -49.1 mV。在持续电流模型中加入一个超慢失活门仅使电位偏移略有减少，降至 -56.6 mV。持续的TTX - R电流还增强了对低于动作电位阈值的去极化输入的反应。此外，持续的TTX - R电流的存在使细胞易于发生阳极破裂兴奋。这些结果表明，虽然持续的TTX - R电流不是动作电位快速去极化阶段的主要贡献者，但它通过调节小DRG神经元的静息电位和对阈下刺激的反应，有助于设定其电生理特性。
