Current and voltage clamp recordings were made with a patch-clamp technique from large, light, dorsal root ganglia (DRG) neurons in tissue culture, derived from trisomy 16 and normal fetal mice. In a Na gradient of [52 mM]o/[28 mM]i, the action potential was accelerated, depolarization and repolarization were faster and the total Na conductance was higher in trisomic neurons. A tetrodotoxin (TTX)-sensitive, fast Na current was demonstrated, about 0.9 nA in trisomic and 0.3 nA in control neurons. The calculated mean specific membrane conductances were 0.74 mS/cm2 and 0.28 mS/cm2, respectively. A TTX-insensitive, slow Na conductance, 3-4 times the fast Na conductance and sensitive to Cd, also was demonstrated, with a 2-fold greater current density and conductance in trisomic as compared with control neurons, of 2.22 +/- 0.54 mS/cm2 and 1.26 +/- 0.09 mS/cm2, respectively. The voltage-dependence and kinetics of the TTX-insensitive, slow, Na current were similar in the two neuronal groups. The results indicate that depolarization during the action potential, in fetal mouse DRG neurons in culture, is mediated by this slow TTX-insensitive Na current. Further, acceleration of depolarization in trisomy 16 neurons is caused by a 2-fold increase in the density of the slow Na current.