Nature Neuroscience
3, 559 - 565 (2000)
doi:10.1038/75729
Cyclic GMP-dependent feedback inhibition of AMPA receptors is independent of PKGSaobo Lei1, Michael F. Jackson1, Zhengping Jia2, John Roder3, Donglin Bai4, Beverley A. Orser4
& John F. MacDonald11
Departments of Physiology and Pharmacology, University of Toronto, Medical Sciences Bldg., 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada
2
Hospital for Sick Children, University of Toronto, 555 University Ave., Toronto, Ontario M5G 1X8, Canada
3
Mt. Sinai Research Institutes, University of Toronto, 600 University Ave., Toronto, Ontario M5G 1X5, Canada
4
Department of Anaesthesia, University of Toronto, Anaesthesia Research Laboratory, 1 King's College Circle, Toronto, Ontario M55 1A8, Canada
Correspondence should be addressed to John F. MacDonald j.macdonald@utoronto.caIn 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.
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