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-gate d sodium channel that is resistant to tetrodotoxin(1-9). We report her e that we have identified a 1,957 aminoacid sodium channel in these ce lls that shows 65% identity with the rat cardiac tetrodotoxin-insensit ive sodium channel(10), and is not expressed in other peripheral and c entral neurons, glia or non-neuronal tissues. In situ hybridization sh ows that the channel is expressed only by small-diameter sensory neuro ns in neonatal and adult dorsal root and trigeminal ganglia. The chann el 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 i nto the spinal cord is resistant to tetrodotoxin(8,11,12), block of ex pression or function of such a C-fibre-restricted sodium channel may h ave a selective analgesic effect.