A novel mechanism of AMPA receptor regulation: ionically triggered kinases and phosphatases.

We have postulated elsewhere (Shaw CA and Lanius RA. Dev Brain Res 70, 153-161 (1992)) that the kinase/phosphatase regulation of AMPA receptors is mediated by specific ions. Using an in vitro cortical slice preparation we have now examined the roles of calcium (Ca2+), chloride (Cl-), potassium (K+), and sodium (Na+) in the regulation of AMPA receptors. Ca2+ led to a concentration-dependent decrease in [3H]-CNQX binding which could be blocked by a general protein kinase inhibitor (H-7) and a protein kinase A inhibiting peptide. Tamoxifen, a relatively specific protein kinase C inhibitor, had no effect. In contrast, Cl- led to concentration-dependent increases in [3H]-CNQX binding which could be blocked by both sodium-ortho-vanadate, a tyrosine residue selective phosphatase inhibitor, and sodium-beta-D-glycerol phosphate, a serine residue selective phosphatase blocker. K+ and Na+ had no effect on [3H]-CNQX binding. These results suggest that Ca2+ and Cl- may be acting as signals which trigger kinase(s) and phosphatase(s) involved in the regulation of AMPA receptors.