TY - JOUR
T1 - β-Adrenergic regulation of synaptic NMDA receptors by cAMP-dependent protein kinase
AU - Raman, Indira M.
AU - Tong, Gang
AU - Jahr, Craig E.
N1 - Funding Information:
We thank J. Volk for preparation of the cell cultures; Drs. J. Galligan and J. Williams for pharmacological advice; Drs. D. Bergles, J. Diamond, J. Dzubay, M. Jones, and J. Scott for helpful discussions and comments on the manuscript; and Dr. Bruce P. Bean for encouraging this collaboration. This work was supported by National Institutes of Health grant NS21419 (C. E. J.).
PY - 1996/2
Y1 - 1996/2
N2 - To identity 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 β-adrenergic receptor agonists norepinephrine and isoproterenol overcame the ability of calcineurin to depress the amplitude of NMDA EPSCs. Thus, stimulation of β-adrenergic receptors during excitatory synaptic transmission can increase charge transfer and Ca2+ influx through NMDA receptors.
AB - To identity 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 β-adrenergic receptor agonists norepinephrine and isoproterenol overcame the ability of calcineurin to depress the amplitude of NMDA EPSCs. Thus, stimulation of β-adrenergic receptors during excitatory synaptic transmission can increase charge transfer and Ca2+ influx through NMDA receptors.
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U2 - 10.1016/S0896-6273(00)80059-8
DO - 10.1016/S0896-6273(00)80059-8
M3 - Article
C2 - 8789956
AN - SCOPUS:0029670940
SN - 0896-6273
VL - 16
SP - 415
EP - 421
JO - Neuron
JF - Neuron
IS - 2
ER -