Differential expression of slow and fast-repriming tetrodotoxin-sensitive sodium currents in dorsal root ganglion neurons

Zhi-Yong Tan; Bin Wu; Xiaolin Su; You Zhou; Yong-Hua Ji

doi:10.3389/fnmol.2023.1336664

Differential expression of slow and fast-repriming tetrodotoxin-sensitive sodium currents in dorsal root ganglion neurons

Front Mol Neurosci. 2024 Jan 11:16:1336664. doi: 10.3389/fnmol.2023.1336664. eCollection 2023.

Authors

Zhi-Yong Tan^#^{1

2}, Bin Wu^#^{2

3}, Xiaolin Su², You Zhou⁴, Yong-Hua Ji⁴

Affiliations

¹ Department of Pathophysiology, Hebei University School of Basic Medicine, Baoding, China.
² Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, United States.
³ Institute of Special Environment Medicine, Nantong University, Nantong, China.
⁴ Department of Physiology, Hebei University School of Basic Medicine, Baoding, China.

^# Contributed equally.

Abstract

Sodium channel Nav1.7 triggers the generation of nociceptive action potentials and is important in sending pain signals under physiological and pathological conditions. However, studying endogenous Nav1.7 currents has been confounded by co-expression of multiple sodium channel isoforms in dorsal root ganglion (DRG) neurons. In the current study, slow-repriming (SR) and fast-repriming (FR) tetrodotoxin-sensitive (TTX-S) currents were dissected electrophysiologically in small DRG neurons of both rats and mice. Three subgroups of small DRG neurons were identified based on the expression pattern of SR and FR TTX-S currents. A majority of rat neurons only expressed SR TTX-S currents, while a majority of mouse neurons expressed additional FR TTX-S currents. ProTx-II inhibited SR TTX-S currents with variable efficacy among DRG neurons. The expression of both types of TTX-S currents was higher in Isolectin B4-negative (IB₄^-) compared to Isolectin B4-positive (IB₄⁺) neurons. Paclitaxel selectively increased SR TTX-S currents in IB₄^- neurons. In simulation experiments, the Nav1.7-expressing small DRG neuron displayed lower rheobase and higher frequency of action potentials upon threshold current injections compared to Nav1.6. The results suggested a successful dissection of endogenous Nav1.7 currents through electrophysiological manipulation that may provide a useful way to study the functional expression and pharmacology of endogenous Nav1.7 channels in DRG neurons.

Keywords: Nav1.7; TTX-sensitive; dorsal root ganglion; isolectin B4; pain; slow-repriming.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Z-YT was supported by Department of Defense Discovery Award (W81XWH-20-1-0138) and Natural Science Foundation of Hebei Province (C2023201035). BW was supported by National Natural Science Foundation of China (82101305).