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

Neuroreport. 1993 Jun;4(6):795-8. doi: 10.1097/00001756-199306000-00050.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • Animals
  • Calcium / metabolism
  • Chlorides / metabolism
  • Glycerophosphates / pharmacology
  • Ibotenic Acid / analogs & derivatives
  • Ibotenic Acid / antagonists & inhibitors
  • In Vitro Techniques
  • Isoquinolines / pharmacology
  • Peptides / pharmacology
  • Phosphoric Monoester Hydrolases / metabolism*
  • Piperazines / pharmacology
  • Potassium / metabolism
  • Protein Kinase Inhibitors
  • Protein Kinases / metabolism*
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA
  • Receptors, Glutamate / metabolism*
  • Sodium / metabolism
  • Tamoxifen / pharmacology
  • Vanadates / pharmacology
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid

Substances

  • Chlorides
  • Glycerophosphates
  • Isoquinolines
  • Peptides
  • Piperazines
  • Protein Kinase Inhibitors
  • Quinoxalines
  • Receptors, AMPA
  • Receptors, Glutamate
  • Tamoxifen
  • protein kinase inhibitor peptide
  • Ibotenic Acid
  • Vanadates
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Sodium
  • Protein Kinases
  • Phosphoric Monoester Hydrolases
  • Potassium
  • Calcium