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

We have examined the distribution of the sensory neuron-specific Na+ channel Na(v)1.8 (SNS/PN3) in nociceptive and non-nociceptive dorsal root ganglion (DRG) neurons and whether its distribution is related to neuronal membrane properties. Na(v)1.8-like immunoreactivity (Na(v)1.8-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-, Adelta- or Aalpha/beta. A significantly higher proportion of nociceptive than low threshold mechanoreceptive (LTM) neurons showed Na(v)1.8-LI, and nociceptive neurons had significantly more intense immunoreactivity in their somata than LTM neurons. Results showed that 89, 93 and 60 % of C-, Adelta and Aalpha/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 Na(v)1.8-LI was also present in some LTM units including a C LTM, all Adelta LTM units (D hair), about 10 % of cutaneous LTM Aalpha/beta-units, but no muscle spindle afferent units. Na(v)1.8-LI intensity was negatively correlated with soma size (all neurons) and with dorsal root CVs in A- but not C-fibre neurons. Na(v)1.8-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 Na(v)1.8 protein may contribute to the longer AP durations (especially in A-fibre neurons) and larger AP overshoots that are typical of nociceptors.