Arachidonic acid potentiates currents through Ca2+-permeable AMPA receptors by interacting with a CaMKII pathway.
The present study investigated the effect of arachidonic acid on the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, presumably heteromeric receptors formed of GluR1, GluR2, and GluR3, expressed in Xenopus oocytes. Arachidonic acid (10 microM) potentiated currents through receptors expressing GluR1 and 3 (GluR1,3) to 170% of basal level during initial 20 min following application, being still evident at 60-min washing-out of the drug, while it never or little enhanced currents through receptors expressing GluR1 and 2 (GluR1,2) or GluR1, 2, and 3 (GluR1,2,3) (110% 30 min after treatment). The effect of arachidonic acid on GluR1,3 currents was not observed in Ca2+-free extracellular solution, and the potentiation was blocked by either KN-93, a selective Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor, or NP217, an active CaMKII inhibitor peptide, when co-expressed with the receptors. In contrast, the protein synthesis inhibitor, cycloheximide, the selective inhibitor of cAMP-dependent protein kinase (PKA), H-89, the selective inhibitors of protein kinase C (PKC), PKCI and GF109203X, the mitogen-activated protein (MAP) kinase kinase inhibitor, PD98059, or the inactive CaMKII inhibitors, KN-92 and NP218, had no effect on the currents. In the assay of intracellular calcium mobilizations, Ca2+ influx in response to receptor activation was greatest with receptors formed in oocytes expressing GluR1,3. The results of the present study indicate that arachidonic acid induces a long-lasting potentiation of GluR1,3 currents, possibly as a result of the interaction with a CaMKII pathway.
Nishizaki
T
T
Department of Physiology, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. tomo@med.kobe-u.ac.jp
Matsuoka
T
T
Nomura
T
T
Enikolopov
G
G
Sumikawa
K
K
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D001596:Benzylamines / Q000494:pharmacology; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology; D007546:Isoquinolines / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D014981:Xenopus; D000096926:Benzenesulfonamides
D016718:Arachidonic Acid; D001596:Benzylamines; D002118:Calcium; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D005419:Flavonoids; D007211:Indoles; D007546:Isoquinolines; D007608:Kainic Acid; D008301:Maleimides; D011493:Protein Kinase C; D012333:RNA, Messenger; D018091:Receptors, AMPA; D013449:Sulfonamides; C104723:glutamate receptor ionotropic, AMPA 3; C072105:KN 93; D000096926:Benzenesulfonamides; C070515:bisindolylmaleimide I; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; C104722:glutamate receptor ionotropic, AMPA 2; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one