Na+-activated K+ channels (KNa) exist in different types of neurones and their activation has been shown to depend on Na+ influx via voltage-activated channels. However, one major route for Na+ influx into neurones is through ionotropic receptors and its role in activating KNa is still unclear. We have examined whether Na+ influx induced by activation of AMPA receptors can activate KNa in lamprey spinal cord neurones. Our results showed that the application of AMPA induced not only the characteristic inward current but also produced an outward current outlasting the activation of the receptors. This outward current was mediated by K+ and was abolished when Na+ was substituted with Li+. The AMPA-mediated KNa current was completely blocked by quinidine but was not modulated by increased intracellular Cl– concentration or ATP. Thus, Na+ influx via AMPA receptor channels activates KNa with properties similar to Slack channels. The AMPA-activated KNa may act as an inherent negative feedback mechanism to regulate the homeostasis of excitation.