Cyclic GMP-dependent feedback inhibition of AMPA receptors is independent of PKG.
In central neurons, the second messenger cGMP is believed to induce long-term changes in efficacy at glutamatergic synapses through activation of protein kinase G (PKG). Stimulating nitric oxide synthase, activating soluble guanylyl cyclase or elevating concentrations of intracellular cGMP depressed excitatory synaptic transmission in CA1 hippocampal neurons. Unexpectedly, intracellular cGMP depressed responses of AMPA receptors and inhibited excitatory postsynaptic currents in hippocampal neurons independently of phosphorylation. Our findings demonstrate that cGMP's modulation of excitatory transmission may involve a coupling of AMPA channel activity to levels of cGMP.
Lei
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Departments of Physiology and Pharmacology, University of Toronto, Medical Sciences Bldg., 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
Jackson
M F
MF
Jia
Z
Z
Roder
J
J
Bai
D
D
Orser
B A
BA
MacDonald
J F
JF
D000818:Animals; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005246:Feedback / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D066298:In Vitro Techniques; D016202:N-Methylaspartate / Q000494:pharmacology; D009433:Neural Inhibition / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D020030:Nitric Oxide Donors; D047428:Protein Kinase Inhibitors; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C016276:8-bromocyclic GMP; D003995:Dibutyryl Cyclic GMP; D018698:Glutamic Acid; D016202:N-Methylaspartate; D019001:Nitric Oxide Synthase; D011494:Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D011493:Protein Kinase C; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517599:Camk1 protein, rat; C517682:Pnck protein, rat; D006152:Cyclic GMP