It is well known that morphological and functional changes during neural differentiation sometimes accompany the expression of various voltage-gated ion channels. In this work, we investigated whether the enhancement of sodium current in differentiated neuroblastoma x glioma NG108-15 cells treated with dibutyryl cAMP is related to the expression of voltage-gated sodium channels. The results were as follows. (1) Sodium current density on peak voltage in differentiated cells was significantly enhanced compared with that in undifferentiated cells, as detected by the whole-cell patch clamp method. The steady-state inactivation curve in differentiated cells was similar to that for undifferentiated cells, but a hyperpolarized shift in the activation curve for differentiated cells was observed. The sodium currents of differentiated and undifferentiated cells were completely inhibited by 10(-7) M tetrodotoxin (TTX). (2) The only Na-V mRNA with an increased expression level during neuronal differentiation was that for Na(V)1.7, as observed by real-time PCR analysis. (3) The increase in the level of Na(V)1.7 alpha subunit expression during neuronal differentiation was also observed by immunocytochemistry; in particular, the localization of Na(V)1.7 alpha subunits on the soma, varicosities and growth cone was significant. These results suggest that the enhancement of TTX-sensitive sodium current density in differentiated NG108-15 cells is mainly due to the increase in the expression of the TTX-sensitive voltage-gated Na+ channel, Na(V)1.7.