Persistent TTX-resistant Na+ current affects resting potential and response to depolarization in simulated spinal sensory neurons

Small dorsal root ganglion (DRG) neurons, which include nociceptors, expres s multiple voltage-gated sodium currents. In addition to a classical fast i nactivating tetrodotoxin-sensitive (TTX-S) sodium current, many of these ce lls express a TTX-resistant (TTX-R) sodium current that activates near -70 mV and is persistent at negative potentials. To investigate the possible co ntributions of this TTX-R persistent (TTX-RP) current to neuronal excitabil ity, we carried out computer simulations using the Neuron program with TTX- S and -RP currents, fit by the Hodgkin-Huxley model, that closely matched t he currents recorded from small DRG neurons. In contrast to fast TTX-S curr ent, which was well fit using a m(3)h model, the persistent TTX-R current w as not well fit by an m3h model and was better fit using an mh model. The p ersistent TTX-R current had a strong influence on resting potential, shifti ng it from -70 to -49.1 mV. Inclusion of an ultra-slow inactivation gate in the persistent current model reduced the potential shift only slightly, to -56.6 mV. The persistent TTX-R current also enhanced the response to depol arizing inputs that were subthreshold for spike electrogenesis. In addition , the presence of persistent TTX-R current predisposed the cell to anode br eak excitation. These results suggest that, while the persistent TTX-R curr ent is not a major contributor to the rapid depolarizing phase of the actio n potential, it contributes to setting the electrogenic properties of small DRG neurons by modulating their resting potentials and response to subthre shold stimuli.