Gating and modulation of presumptive NaV1.9 channels in enteric and spinal sensory neurons

被引:102
作者
Coste, B [1 ]
Osorio, N [1 ]
Padilla, F [1 ]
Crest, M [1 ]
Delmas, P [1 ]
机构
[1] CNRS, Integrat Informat Sensorielles, UMR 6150, Fac Med,IFR Jean Roche, F-13916 Marseille 20, France
关键词
D O I
10.1016/j.mcn.2004.01.015
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The Na(V)1.9 subunit is expressed in nociceptive dorsal root ganglion (DRG) neurons and sensory myenteric neurons in which it generates 'persistent' tetrodotoxin-resistant (TTX-R) Na+ currents of yet unknown physiological functions. Here, we have analyzed these currents in details by combining single-channel and whole-cell recordings from cultured rat DRG and myenteric neurons. Comparison of single-channel with whole-cell data indicates that recording using internal CsCl best reflects the basic electrical features of Na(V)1.9 currents. Inclusion of fluoride in the pipette solution caused a negative shift in the activation and inactivation gates of Na(V)1.9 but not Na(V)1.8. Fluoride acts by promoting entry of Na(V)1.9 channels into a preopen closed state, which causes a strong bias towards opening and enhances the ability of sensory neurons to sustain spiking. Thus, the modulation of the resting-closed states of Na(V)1.9 channels strongly influences nociceptor excitability and may provide a mechanism by which inflammatory mediators alter pain threshold. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:123 / 134
页数:12
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