Na+-activated K+ currents (K(Na)) have been reported in multiple neuronal nuclei and the properties of K(Na) vary in different cell types. We have described previously the distribution of Slack, a Na+-activated K+ channel subunit. Another recently cloned Na+-activated K+ channel is Slick, which differs from Slack in its rapid activation and its sensitivity to intracellular ATP levels. We now report the localization of Slick in the rat central nervous system using in situ and immunohistochemical techniques. As for Slack, we find that Slick is widely distributed in the brain. Specifically, strong hybridization signals and immunoreactivity were found in the brainstem, including auditory neurons such as the medial nucleus of the trapezoid body. As has also been shown for Slack, Slick is expressed in the olfactory bulb, red nucleus, facial nucleus, pontine nucleus, oculomotor nucleus, substantia nigra, deep cerebellar nuclei, vestibular nucleus, and the thalamus. Slick mRNA and protein, however, also are found in certain neurons that do not express Slack. These neurons include those of the hippocampal CA1, CA2, and CA3 regions, the dentate gyrus, supraoptic nucleus, hypothalamus, and cortical layers II, III, and V. These data suggest that Slick may function independently of Slack in these regions. Computer simulations indicate that Slick currents can cause adaptation during prolonged stimuli. Such adaptation allows a neuron to respond to high-frequency stimulation with lower-frequency firing that remains temporally locked to individual stimuli, a property seen in many auditory neurons. Although it is not yet known if Slick and Slack subunits heteromultimerize, the existence of two genes that encode K(Na), that are widely expressed in the nervous system, with both overlapping and nonoverlapping distributions, provides the basis for the reported heterogeneity in the properties of K(Na) from various neurons.