Through their repetitive discharge, GABAergic neurons of the substantia nigra pars reticulata (SNr) tonically inhibit the target nuclei of the basal ganglia and the dopamine neurons of the midbrain. As the repetitive firing of SNr neurons persists in vitro, perforated, whole-cell and cell-attached patch-clamp recordings were made from rat brain slices to determine the mechanisms underlying this activity. The spontaneous activity of SNr neurons was not perturbed by the blockade of fast synaptic transmission, demonstrating that it was autonomous in nature. A subthreshold, slowly inactivating, voltage-dependent, tetrodotoxin (TTX)-sensitive Na+ current and a TTX-insensitive inward current that was mediated in part by Na+ were responsible for depolarization to action potential (AP) threshold. An apamin-sensitive spike afterhyperpolarization mediated by small-conductance Ca2+-dependent K+ (SK) channels was critical for the precision of autonomous activity. SK channels were activated, in part, by Ca(2+) flowing throughomega-conotoxin GVIA-sensitive, class 2.2 voltage-dependent Ca2+ channels. Although Cs+/ZD7288 (4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium chloride)-sensitive hyperpolarization-activated currents were also observed in SNr neurons, they were activated at voltages that were in general more hyperpolarized than those associated with autonomous activity. Simultaneous somatic and dendritic recordings revealed that autonomously generated APs were observed first at the soma before propagating into dendrites up to 120 microm from the somatic recording site. Backpropagation of autonomously generated APs was reliable with no observable incidence of failure. Together, these data suggest that the resting inhibitory output of the basal ganglia relies, in large part, on the intrinsic firing properties of the neurons that convey this signal.