Potassium channels play an important role in controlling neuronal firing and synaptic interactions. Na(+)-activated K(+) (K(Na)) channels have been shown to exist in neurons in different regions of the CNS, but their physiological function has been difficult to assess. In this study, we have examined if neurons in the spinal cord possess K(Na) currents. We used whole cell recordings from isolated spinal cord neurons in lamprey. These neurons display two different K(Na) currents. The first was transient and activated by the Na(+) influx during the action potentials, and it was abolished when Na(+) channels were blocked by tetrodotoxin. The second K(Na) current was sustained and persisted in tetrodotoxin. Both K(Na) currents were abolished when Na(+) was substituted with choline or N-methyl-D-glucamine, indicating that they are indeed dependent on Na(+) influx into neurons. When Na(+) was substituted with Li(+), the amplitude of the inward current was unchanged, whereas the transient K(Na) current was reduced but not abolished. This suggests that the transient K(Na) current is partially activated by Li(+). These two K(Na) currents have different roles in controlling the action potential waveform. The transient K(Na) appears to act as a negative feedback mechanism sensing the Na(+) influx underlying the action potential and may thus be critical for setting the amplitude and duration of the action potential. The sustained K(Na) current has a slow kinetic of activation and may underlie the slow Ca(2+)-independent afterhyperpolarization mediated by repetitive firing in lamprey spinal cord neurons.