Developmental expression of the TTX-resistant voltage-gated sodium channels Na(v)1.8 (SNS) and Na(v)1.9 (SNS2) in primary sensory neurons

The development of neuronal excitability involves the coordinated expressio n of different voltage-gated ion channels. We have characterized the expres sion of two sensory neuron-specific tetrodotoxin-resistant sodium channel a lpha subunits, Na(v)1. (SNS/PN3) and Na(v)1.9 (SNS2/NaN), in developing rat lumbar dorsal root ganglia (DRGs). Expression of both Na(v)1.8 and Na(v)1. 9 increases with age, beginning at embryonic day (E) 15 and E17, respective ly, and reaching adult levels by postnatal day 7. Their distribution is res tricted mainly to those subpopulations of primary sensory neurons in develo ping and adult DRGs that give rise to unmyelinated C-fibers (neurofilament 200 negative). Na(v)1.8 is expressed in a higher proportion of neuronal pro files than Na(v)1.9 at all stages during development, as in the adult. At E 17, almost all Na(v)1.8-expressing neurons also express the high-affinity N GF receptor TrkA, and only a small proportion bind to IB4, a marker for c-r et-expressing (glial-derived neurotrophic factor-responsive) neurons. Becau se IB4 binding neurons differentiate from TrkA neurons in the postnatal per iod, the proportion of Na(v)1.8 cells that bind to IB4 increases, in parall el with a decrease in the proportion of Na(v)1.8-TrkA co-expressing cells. In contrast, an equal number of Na(v)1.9 cells bind IB4 and TrkA in embryon ic life. The differential expression of Na(v)1.8 and Na(v)1.9 in late embry onic development, with their distinctive kinetic properties, may contribute to the development of spontaneous and stimulus-evoked excitability in smal l diameter primary sensory neurons in the perinatal period and the activity -dependent changes in differentiation they produce.