Beta-adrenergic regulation of synaptic NMDA receptors by cAMP-dependent protein kinase.
To identify the protein kinases regulating synaptic NMDA receptors, as well as the conditions favoring enhancement of NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) by phosphorylation, we studied the effects of kinase activation and inhibition in hippocampal neurons. Inhibition of cAMP-dependent protein kinase (PKA) prevented recovery of NMDA receptors from calcineurin-mediated dephosphorylation induced by synaptic activity, suggesting that tonically active PKA phosphorylates receptors during quiescent periods. Conversely, elevation of PKA activity by forskolin, cAMP analogs, or the beta-adrenergic receptor agonists norepinephrine and isoproterenol overcame the ability of calcineurin to depress the amplitude of NMDA EPSCs. Thus, stimulation of beta-adrenergic receptors during excitatory synaptic transmission can increase charge transfer and Ca2+ influx through NMDA receptors.
Raman
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IM
Vollum Institute Oregon Health Sciences University, Portland 97201, USA.
Tong
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G
Jahr
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CE
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D010749:Phosphoprotein Phosphatases / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D002148:Calmodulin-Binding Proteins; D011943:Receptors, Adrenergic, beta; D016194:Receptors, N-Methyl-D-Aspartate; D005576:Colforsin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases