DISTRIBUTION OF THE TETRODOTOXIN-RESISTANT SODIUM-CHANNEL PN3 IN RAT SENSORY NEURONS IN NORMAL AND NEUROPATHIC CONDITIONS

The novel sodium channel PN3/alpha-SNS, which was cloned from a rat do rsal root ganglion (DRG) cDNA library, is expressed predominantly in s mall sensory neurons and may contribute to the tetrodotoxin-resistant (TTXR) sodium current that is believed to be associated with central s ensitization in chronic neuropathic pain states. To assess further the role of PN3, we have used electrophysiological, in situ hybridization and immunohistochemical methods to monitor changes in TTXR sodium cur rent and the distribution of PN3 in normal and peripheral nerve-injure d rats. (1) Whole-cell patch-clamp recordings showed that there were n o significant changes in the TTXR and TTX-sensitive sodium current den sities of small DRG neurons after chronic constriction injury (CCl) of the sciatic nerve. (2) Additionally, in situ hybridization showed tha t there was no change in the expression of PN3 mRNA in the DRG up to 1 4 d after CCl. PN3 mRNA was not detected in sections of brain and spin al cord taken from either normal or nerve-injured rats. (3) In contras t, immunohistochemical studies showed that major changes in the subcel lular distribution of PN3 protein were caused by either CCl or complet e transection of the sciatic nerve. The intensity of PN3 immunolabelin g decreased in small DRG neurons and increased in sciatic nerve axons at the site of injury. The alteration in immunolabeling was attributed to translocation of presynthesized, intracellularly located PN3 prote in from neuronal somata to peripheral axons, with subsequent accumulat ion at the site of injury. The specific subcellular redistribution of PN3 after peripheral nerve injury may be an important factor in establ ishing peripheral nerve hyperexcitability and resultant neuropathic pa in.