Dopamine (DA) neurons and GABA neurons of the substantia nigra (SN) promote distinct functions in the control of movement and have different firing properties and action potential (AP) waveforms. APs recorded from DA and GABA neurons differed in amplitude, maximal rate of rise, and duration. In addition, the threshold potential for APs was higher in DA neurons than in GABA neurons. The activation of voltage-gated Na(+) channels accounts largely for these differences as the application of a low concentration of the voltage-gated Na(+) channel blocker TTX had an effect on all of these parameters. We have examined functional properties of somatic Na(+) channels in nucleated patches isolated from DA and GABA neurons. Peak amplitudes of macroscopic Na(+) currents were smaller in DA neurons in comparison to those in GABA neurons. The mean peak Na(+) conductance density was 24.5 pS microm(-2) in DA neurons and almost twice as large, 41.6 pS microm(-2), in GABA neurons. The voltage dependence of Na(+) channel activation was not different between the two types of SN neurons. Na(+) channels in DA and GABA neurons, however, differed in the voltage dependence of inactivation, the mean mid-point potential of steady-state inactivation curve being more positive in DA neurons than in GABA neurons. The results suggest that specific Na(+) channel gating properties and Na(+) conductance densities in the somatic membrane of SN neurons may have consequences on synaptic signal integration in the soma of both types of neurons and on somatodendritic release of dopamine by DA neurons.