Sodium channel Na_v1.8 requires stronger depolarization than other sodium channels for activation and inactivation. The contribution of Na_v1.8 C-terminus to this property was investigated by producing Na_v1.8 and Na_v1.4 chimeras and expressing them in ND7/23 cells. Current densities of the chimeras were significantly different than in parental channels, and the voltage-dependence of activation was depolarized in Na_v1.4/1.8C compared to Na_v1.4. Analysis of steady-state inactivation showed that only Na_v1.8 and Na_v1.4/1.8C currents demonstrate a non-inactivated fraction. Thus, the C-terminus of Na_v1.8 contributes to regulation of channel density at the cell surface, modulates channel gating, and regulates the generation of sustained current.