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 studi ed the effects of kinase activation and inhibition in hippocampal neur ons. Inhibition of cAMP-dependent protein kinase (PKA) prevented recov ery of NMDA receptors from calcineurin-mediated dephosphorylation indu ced by synaptic activity, suggesting that tonically active PKA phospho rylates receptors during quiescent periods. Conversely, elevation of P KA activity by forskolin, cAMP analogs, or the beta-adrenergic recepto r agonists norepinephrine and isoproterenol overcame the ability of ca lcineurin 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.