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.
Lanius
R A
RA
Department of Neuroscience, University of British Columbia, Vancouver, Canada.
Pasqualotto
B A
BA
Shaw
C A
CA
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D005994:Glycerophosphates / Q000494:pharmacology; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA; D017470:Receptors, Glutamate / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D014638:Vanadates / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D002712:Chlorides; D005994:Glycerophosphates; D007546:Isoquinolines; D010455:Peptides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011810:Quinoxalines; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D013629:Tamoxifen; C061479:protein kinase inhibitor peptide; D007051:Ibotenic Acid; D014638:Vanadates; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D012964:Sodium; D011494:Protein Kinases; D010744:Phosphoric Monoester Hydrolases; D011188:Potassium; D002118:Calcium