Cultured mouse cortical astrocytes of the stellate type were studied by using the patch-clamp technique in whole-cell configuration. The astrocytes express at least two types of outwardly rectifying K+ channels which mediate a transient and a sustained current. Activation of AMPA receptors by kainate leads to a substantial blockade of both types of K+ currents. The blockade is absent when Na+ is withdrawn from the external medium, suggesting that it is caused by constant Na+ influx through AMPA receptors. The presence of high Na+ solutions in the pipette induces a blockade of both K+ currents which is very similar to the blockade induced by kainate, supporting thus the view that the mechanism of the blockade of K+ channels by kainate involves Na+ increases in the submembrane area. The blockade occurs between 20 and 40 mM [Na+]i, which is within the physiological range of [Na+]i in astrocytes. The data may suggest that the blockade of K+ channels by high [Na+]i conditions could provide a mechanism to prevent K+ leakage from the astrocytes into the extracellular space during periods of intense neuronal activity.