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 recept ors is mediated by specific ions. Using an in vitro cortical slice pre paration we have now examined the roles of calcium (Ca2+), chloride (C l-), potassium (K+), and sodium (Na+) in the regulation of AMPA recept ors. Ca2+ led to a concentration-dependent decrease in [H-3]-CNQX bind ing which could be blocked by a general protein kinase inhibitor (H-7) and a protein kinase A inhibiting peptide. Tamoxifen, a relatively sp ecific protein kinase C inhibitor, had no effect. In contrast, Cl- led to concentration-dependent increases in [H-3]-CNQX binding which coul d be blocked by both sodium-ortho-vanadate, a tyrosine residue selecti ve phosphatase inhibitor, and sodium-beta-D-glycerol phosphate, a seri ne residue selective phosphatase blocker. K+ and Na+ had no effect on [H-3]-CNQX binding. These results suggest that Ca2+ and Cl- may be act ing as signals which trigger kinase(s) and phosphatase(s) involved in the regulation of AMPA receptors.