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

Authors
Journal
Molecular and Cellular Neuroscience
1044-7431
Publisher
Elsevier
Publication Date
Volume
26
Issue
1
Identifiers
DOI: 10.1016/j.mcn.2004.01.015
Disciplines
  • Biology

Abstract

Abstract The Na V1.9 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 V1.9 currents. Inclusion of fluoride in the pipette solution caused a negative shift in the activation and inactivation gates of Na V1.9 but not Na V1.8. Fluoride acts by promoting entry of Na V1.9 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 V1.9 channels strongly influences nociceptor excitability and may provide a mechanism by which inflammatory mediators alter pain threshold.

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