Tetrodotoxin-sensitive and -resistant Na + channel currents in subsets of small sensory neurons of rats

Abstract

Voltage-activated Na + channels in the primary sensory neurons are important for generation of action potentials and regulation of neurotransmitter release. The Na + channels expressed in different types of dorsal root ganglion (DRG) neurons are not fully known. In this study, we determined the possible difference in tetrodotoxin-sensitive (TTX-S) and -resistant (TTX-R) Na + channel currents between isolectin B4 (IB 4)-positive and IB 4-negative small DRG neurons. Whole-cell voltage- and current-clamp recordings were performed in acutely isolated DRG neurons labeled with and without IB 4 conjugated to Alexa Fluor 594. The peak Na + current density was significantly higher in IB 4-negative than IB 4-positive DRG neurons. While all the IB 4-negative neurons had a prominent TTX-S Na + current, the TTX-R Na + current was present in most IB 4-positive cells. Additionally, the evoked action potential had a higher activation threshold and a longer duration in IB 4-positive than IB 4-negative neurons. TTX had no effect on the evoked action potential in IB 4-positive neurons, but it inhibited the action potential generation in about 50% IB 4-negative neurons. This study provides complementary new information that there is a distinct difference in the expression level of TTX-S and TTX-R Na + channels between IB 4-negative than IB 4-positive small-diameter DRG neurons. This difference in the density of TTX-R Na + channels is responsible for the distinct membrane properties of these two types of nociceptive neurons.