Regulation of kainate receptors by cAMP-dependent protein kinase and phosphatases.
In the mammalian central nervous system, receptors for excitatory amino acid neurotransmitters such as the alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA)-kainate receptor mediate a large fraction of excitatory transmission. Currents induced by activation of the AMPA-kainate receptor were potentiated by agents that specifically stimulate adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase A (PKA) activity or were supported by intracellular application of the catalytic subunit of PKA by itself or in combination with cAMP. Furthermore, depression of these currents by a competitive inhibitor of PKA indicates that AMPA-kainate receptors are regulated by endogenous PKA. Endogenous protein phosphatases also regulate these receptors because an inhibitor of cellular phosphates enhanced kainate currents. Modulation of PKA and phosphatases may regulate the function of these receptors and thus contribute to synaptic plasticity in hippocampal neurons.
Wang
L Y
LY
Department of Physiology, University of Toronto, Ontario, Canada.
Salter
M W
MW
MacDonald
J F
JF
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology / Q000502:physiology; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005333:Fetus; D006624:Hippocampus / Q000502:physiology*; D006706:Homeostasis; D007608:Kainic Acid / Q000378:metabolism*; D007700:Kinetics; D046911:Macromolecular Substances; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*
D000242:Cyclic AMP; D004988:Ethers, Cyclic; D007608:Kainic Acid; D046911:Macromolecular Substances; D016202:N-Methylaspartate; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter