Beta-adrenergic regulation of synaptic NMDA receptors by cAMP-dependent protein kinase

Neuron. 1996 Feb;16(2):415-21. doi: 10.1016/s0896-6273(00)80059-8.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Calcineurin
  • Calmodulin-Binding Proteins / pharmacology
  • Colforsin / pharmacology
  • Cyclic AMP / analogs & derivatives
  • Cyclic AMP-Dependent Protein Kinases / physiology*
  • Electrophysiology
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Hippocampus / physiology
  • Neurons / metabolism
  • Neurons / physiology
  • Phosphoprotein Phosphatases / pharmacology
  • Phosphorylation / drug effects
  • Rats
  • Receptors, Adrenergic, beta / physiology*
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Synapses / metabolism*


  • Adrenergic beta-Agonists
  • Calmodulin-Binding Proteins
  • Receptors, Adrenergic, beta
  • Receptors, N-Methyl-D-Aspartate
  • Colforsin
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Calcineurin
  • Phosphoprotein Phosphatases