Ontogenic development of the TTX-sensitive and TTX-insensitive Na + channels in neurons of the rat dorsal root ganglia

Abstract

Developmental changes in the sensitivity of neurons to tetrodotoxin (TTX) were studied in relation to the cell size in rat dorsal root ganglia (DRG). Na + currents were recorded from neurons of various stages of development. Two types of Na + channels were identified on the basis of their sensitivity to TTX. One type was insensitive to a very high concentration (0.1 mM) of TTX, while the other type was blocked by a low concentration (1 nM) of TTX. These two types of Na + channels were observed throughout the developmental stages examined from day 17 of gestation and adulthood. Thus, both types of Na + channels are already established at the early stage of neuronal development and appear to be retained throughout the life-span of the DRG neuron. The concentration-response relationships for the block of TTX-sensitive Na + current by TTX did not appreciably change during development. Although two types of Na + channels had strikingly different kinetic properties,of each channel type were basically similar throughout development. The TTX-sensitive Na + channels were mainly concentrated in cells with large cell diameters throughout developmental stages examined. These large cells appear to correspond to the ‘large-light’ cells. On the contrary, the TTX-insensitive Na + channels were found in smaller diameter cells which may correspond to the ‘small-dark’ cells. Thus, it is concluded that there are heterogeneous categories of neurons which have Na + channels with different physiological and pharmacological properties. Since Na + channels play a pivotal role in the action potential generation, these heterogeneity of DRG neurons appear to be instrumental in integrating the sensory signals.