A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons

DORSAL root ganglion sensory neurons associated with C-fibres, many of which are activated by tissue-damage, express an unusual voltage-gated sodium channel that is resistant to tetrodotoxin(1-9). We report here that we have identified a 1,957 aminoacid sodium channel in these cells that shows 65% identity with the rat cardiac tetrodotoxin-insensitive sodium channel(10), and is not expressed in other peripheral and central neurons, glia or non-neuronal tissues. In situ hybridization shows that the channel is expressed only by small-diameter sensory neurons in neonatal and adult dorsal root and trigeminal ganglia. The channel is resistant to tetrodotoxin when expressed in Xenopus oocytes. The electrophysiological and pharmacological properties of the expressed channel are similar to those described for the small-diameter sensory neuron tetrodotoxin-resistant sodium channels. As some noxious input into the spinal cord is resistant to tetrodotoxin(8,11,12), block of expression or function of such a C-fibre-restricted sodium channel may have a selective analgesic effect.