Single-cell analysis of sodium channel expression in dorsal root ganglion neurons

被引:116
作者
Ho, Cojen [1 ]
O'Leary, Michael E. [1 ]
机构
[1] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA
关键词
Sodium channel; Dorsal root ganglia; Single-cell RT-PCR; Necl-1; NF200; Peripherin; PRIMARY AFFERENT NEURONS; PRIMARY SENSORY NEURONS; CONDUCTION-VELOCITY; NEUROFILAMENT IMMUNOREACTIVITY; INFLAMMATORY PAIN; RAT; NA(V)1.8; ROLES; NAN; SNS;
D O I
10.1016/j.mcn.2010.08.017
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Sensory neurons of the dorsal root ganglia (DRG) express multiple voltage-gated sodium (Na) channels that substantially differ in gating kinetics and pharmacology. Small-diameter (<25 mu m) neurons isolated from the rat DRG express a combination of fast tetrodotoxin-sensitive (TTX-S) and slow TTX-resistant (TTX-R) Na currents while large-diameter neurons (>30 mu m) predominately express fast TTX-S Na current. Na channel expression was further investigated using single-cell RT-PCR to measure the transcripts present in individually harvested DRG neurons. Consistent with cellular electrophysiology, the small neurons expressed transcripts encoding for both TTX-S (Nav1.1, Nav1.2, Nav1.6, and Nav1.7) and TTX-R (Nav1.8 and Nav1.9) Na channels. Nav1.7, Nav1.8 and Nav1.9 were the predominant Na channels expressed in the small neurons. The large neurons highly expressed TTX-S isoforms (Nav1.1, Nav1.6, and Nav1.7) while TTX-R channels were present at comparatively low levels. A unique subpopulation of the large neurons was identified that expressed TTX-R Na current and high levels of Nav1.8 transcript. DRG neurons also displayed substantial differences in the expression of neurofilaments (NF200, peripherin) and Necl-1, a neuronal adhesion molecule involved in myelination. The preferential expression of NF200 and Necl-1 suggests that large-diameter neurons give rise to thick myelinated axons. Small-diameter neurons expressed peripherin, but reduced levels of NF200 and Necl-1, a pattern more consistent with thin unmyelinated axons. Single-cell analysis of Na channel transcripts indicates that TTX-S and TTX-R Na channels are differentially expressed in large myelinated (Nav1.1, Nav1.6, and Nav1.7) and small unmyelinated (Nav1.7, Nav1.8, and Nav1.9) sensory neurons. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:159 / 166
页数:8
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