Regulation of GABAA and AMPA receptors by agonist and depolarizing stimulation requires phosphatase or kinase activity.

Using a live in vitro slice preparation of adult rat neocortex we have examined the role of phosphorylation and dephosphorylation in the regulation of GABAA and AMPA receptors. Alkaline phosphatase increased binding levels for both receptors while protein kinase A had the opposite effect. For both receptor populations, phosphatase effects were blocked by sodium beta-D-glycerol phosphate and sodium vanadate (phosphatase inhibitors) while kinase actions were blocked by a protein kinase inhibitor. Increases in cell depolarizations by veratridine led to an increase in labelled GABAA receptors, but to decreases in labelled AMPA receptors. Increases in binding were differentially blocked by the two phosphatase inhibitors, sodium beta-D-glycerol phosphate and sodium vanadate while decreases in binding were blocked by protein kinase inhibitor. Agonist stimulation of GABAA and AMPA receptors led to a decrease in receptor binding which could be blocked in both cases by protein kinase inhibitor. These data show that certain cortical excitatory and inhibitory amino acid receptors can be regulated by the action of phosphorylating/dephosphorylating enzymes and further suggest that the regulation induced by cell depolarization and agonist stimulation is based on similar mechanisms.