AMPA/kainate receptor activation blocks K+ currents via internal Na+ increase in mouse cultured stellate astrocytes.
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 The blockade is absent when Na+ is withdrawn from the external medium, suggesting that it is caused by constant Na+ influx through AMPA receptors.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.
Robert
A
A
Département de Pharmacologie, Centre Médical Universitaire, Genève, Switzerland.
Magistretti
P J
PJ
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D001464:Barium / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000096:biosynthesis / Q000502:physiology; D018091:Receptors, AMPA / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000378:metabolism* / Q000494:pharmacology
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018091:Receptors, AMPA; D001464:Barium; D012964:Sodium; D007608:Kainic Acid