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First published online on June 6, 2003.
Copyright © 2003 by The Physiological Society
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Received February 21, 2003
Accepted after revision May 2, 2003

The TTX-resistant sodium channel Nav1.8 (SNS/PN3): expression and correlation with membrane properties in rat nociceptive primary afferent neurons

Laiche Djouhri1, Xin Fang1, Kenji Okuse2, John N. Wood2, Carol M. Berry1, and S. Lawson3*

1 Department of Physiology, University of Bristol Medical School, Bristol BS8 1TD, UK
2 Department of Biology, University College London, Gower Street, London WC1E 6BT, UK
3 Department of Physiology, University of Bristol, Medical School, University Walk, Bristol BS8 1TD, UK

* To whom correspondence should be addressed. E-mail: sally.lawson{at}bristol.ac.uk.

We have examined the distribution of the sensory neuron-specific Na+ channel Nav1.8 (SNS/PN3) in nociceptive and non-nociceptive dorsal root ganglion (DRG) neurons and whether its distribution is related to neuronal membrane properties. Nav1.8-like immunoreactivity (Nav1.8-LI) was examined with an affinity purified polyclonal antiserum (SNS11) in rat DRG neurons that were classified according to sensory receptive properties and by conduction velocity (CV) as C-, Ad[%%%]- or A{alpha}/{beta}. A significantly higher proportion of nociceptive than low threshold mechanoreceptive (LTM) neurons showed Nav1.8-LI, and nociceptive neurons had significantly more intense immunoreactivity in their somata than LTM neurons. Results showed that 89, 93 and 60 % of C-, Ad[%%%]- and A{alpha}/{beta}-fibre nociceptive units respectively and 88 % of C-unresponsive units were positive. C-unresponsive units had electrical membrane properties similar to C-nociceptors and were considered to be nociceptive-type neurons. Weak positive Nav1.8-LI was also present in some LTM units including a C LTM, all Ad[%%%] LTM units (D hair), about 10 % of cutaneous LTM A{alpha}/{beta}-units, but no muscle spindle afferent units. Nav1.8-LI intensity was negatively correlated with soma size (all neurons) and with dorsal root CVs in A- but not C-fibre neurons. Nav1.8-LI intensity was positively correlated with action potential (AP) duration (both rise and fall time) in A-fibre neurons and with AP rise time only in positive C-fibre neurons. It was also positively correlated with AP overshoot in positive neurons. Thus high levels of Nav1.8 protein may contribute to the longer AP durations (especially in A-fibre neurons) and larger AP overshoots that are typical of nociceptors.




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