Liu Xiao-Ping, Wooltorton Julian R A, Gaboyard-Niay Sophie, Yang Fu-Chia, Lysakowski Anna, Eatock Ruth Anne
Speech and Hearing Bioscience and Technology Program, Harvard-Massachusetts Institute of Technology Health Sciences and Technology Program, Cambridge, Massachusetts; Eaton-Peabody Laboratories, Massachusetts Eye and Ear, and Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts;
Otorhinolaryngology and Neuroscience, Baylor College of Medicine, Houston, Texas;
J Neurophysiol. 2016 May 1;115(5):2536-55. doi: 10.1152/jn.00902.2015. Epub 2016 Mar 2.
Firing patterns differ between subpopulations of vestibular primary afferent neurons. The role of sodium (NaV) channels in this diversity has not been investigated because NaV currents in rodent vestibular ganglion neurons (VGNs) were reported to be homogeneous, with the voltage dependence and tetrodotoxin (TTX) sensitivity of most neuronal NaV channels. RT-PCR experiments, however, indicated expression of diverse NaV channel subunits in the vestibular ganglion, motivating a closer look. Whole cell recordings from acutely dissociated postnatal VGNs confirmed that nearly all neurons expressed NaV currents that are TTX-sensitive and have activation midpoints between -30 and -40 mV. In addition, however, many VGNs expressed one of two other NaV currents. Some VGNs had a small current with properties consistent with NaV1.5 channels: low TTX sensitivity, sensitivity to divalent cation block, and a relatively negative voltage range, and some VGNs showed NaV1.5-like immunoreactivity. Other VGNs had a current with the properties of NaV1.8 channels: high TTX resistance, slow time course, and a relatively depolarized voltage range. In two NaV1.8 reporter lines, subsets of VGNs were labeled. VGNs with NaV1.8-like TTX-resistant current also differed from other VGNs in the voltage dependence of their TTX-sensitive currents and in the voltage threshold for spiking and action potential shape. Regulated expression of NaV channels in primary afferent neurons is likely to selectively affect firing properties that contribute to the encoding of vestibular stimuli.
前庭初级传入神经元亚群之间的放电模式存在差异。由于据报道啮齿动物前庭神经节神经元（VGNs）中的钠（NaV）电流是均匀的，且大多数神经元NaV通道具有电压依赖性和河豚毒素（TTX）敏感性，因此尚未研究NaV通道在这种多样性中的作用。然而，逆转录聚合酶链反应（RT-PCR）实验表明前庭神经节中存在多种NaV通道亚基的表达，这促使我们进一步研究。对新生VGNs进行急性解离后的全细胞记录证实，几乎所有神经元都表达对TTX敏感且激活中点在-30至-40 mV之间的NaV电流。然而，除此之外，许多VGNs还表达另外两种NaV电流中的一种。一些VGNs有一小部分电流，其特性与NaV1.5通道一致：TTX敏感性低、对二价阳离子阻断敏感以及电压范围相对为负，并且一些VGNs显示出NaV1.5样免疫反应性。其他VGNs有一个具有NaV1.8通道特性的电流：高TTX抗性、时间进程缓慢以及电压范围相对去极化。在两个NaV1.8报告基因系中，VGNs的亚群被标记。具有类似NaV1.8的TTX抗性电流的VGNs在其TTX敏感电流的电压依赖性、放电电压阈值和动作电位形状方面也与其他VGNs不同。初级传入神经元中NaV通道的调节表达可能会选择性地影响有助于前庭刺激编码的放电特性。
