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

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.