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The Journal of Neuroscience, September 1, 2002, 22(17):7425-7433

The Presence and Role of the Tetrodotoxin-Resistant Sodium Channel Na_v1.9 (NaN) in Nociceptive Primary Afferent Neurons

Xin Fang¹, Laiche Djouhri¹, Joel A. Black^{2, 3}, Sulayman D. Dib-Hajj^{2, 3}, Stephen G. Waxman^{2, 3}, and Sally N. Lawson¹

¹ Department of Physiology, University of Bristol, Medical School, Bristol BS8 1TD, United Kingdom, ² Department of Neurology and Paralyzed Veterans of America/Eastern Paralyzed Veterans Association Neuroscience Research Center, Yale University School of Medicine, New Haven, Connecticut 06510, and ³ Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut 06516

This is the first examination of sensory receptive properties and associated electrophysiological properties in vivo of dorsal root ganglion (DRG) neurons that express the TTX-resistant sodium channel Na_v1.9 (NaN). Intracellular recordings in lumbar DRGs in Wistar rats enabled units with dorsal root C-, A-, or A/-fibers to be classified as nociceptive, low-threshold mechanoreceptive (LTM), or unresponsive. Intracellular dye injection enabled subsequent immunocytochemistry for Na_v1.9-like immunoreactivity (Na_v1.9-LI).

Na_v1.9-LI was expressed selectively in nociceptive-type (C- and A-fiber nociceptive and C-unresponsive) units. Of the nociceptive units, 64, 54, and 31% of C-, A-, and A/-fiber units, respectively, were positive for Na_v1.9-LI. C-unresponsive units were included in the nociceptive-type group on the basis of their nociceptor-like membrane properties; 91% were positive. Na_v1.9-LI was undetectable in A- or A/-fiber LTM units and in one C-LTM unit. Na_v1.9-LI intensity was correlated negatively with soma size and conduction velocity in nociceptive units and with conduction velocity in C-fiber units. There was a positive correlation with action potential rise time in nociceptive-type units with membrane potentials equal to or more negative than -50 mV. The data provide direct evidence that Na_v1.9 is expressed selectively in (but not in all) C- and A-fiber nociceptive-type units and suggest that Na_v1.9 contributes to membrane properties that are typical of nociceptive neurons.

Key words: action potential; conduction velocity; DRG; Na_v1.9 (NaN); pain; sodium channel

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22177425-09$05.00/0

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