β-Adrenergic regulation of synaptic NMDA receptors by cAMP-dependent protein kinase

Indira M. Raman, Gang Tong, Craig Jahr

Research output: Contribution to journalArticle

238 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)415-421
Number of pages7
JournalNeuron
Volume16
Issue number2
DOIs
StatePublished - Feb 1996

Fingerprint

Neurotransmitter Receptor
Cyclic AMP-Dependent Protein Kinases
N-Methyl-D-Aspartate Receptors
Adrenergic Agents
Protein Kinases
Calcineurin
Excitatory Postsynaptic Potentials
Adrenergic Agonists
Colforsin
N-Methylaspartate
Isoproterenol
Synaptic Transmission
Adrenergic Receptors
Norepinephrine
Phosphotransferases
Phosphorylation
Neurons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

β-Adrenergic regulation of synaptic NMDA receptors by cAMP-dependent protein kinase. / Raman, Indira M.; Tong, Gang; Jahr, Craig.

In: Neuron, Vol. 16, No. 2, 02.1996, p. 415-421.

Research output: Contribution to journalArticle

Raman, Indira M. ; Tong, Gang ; Jahr, Craig. / β-Adrenergic regulation of synaptic NMDA receptors by cAMP-dependent protein kinase. In: Neuron. 1996 ; Vol. 16, No. 2. pp. 415-421.
@article{8f60ac48c57d49469896df1e5ae77ea6,
title = "β-Adrenergic regulation of synaptic NMDA receptors by cAMP-dependent protein kinase",
abstract = "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.",
author = "Raman, {Indira M.} and Gang Tong and Craig Jahr",
year = "1996",
month = "2",
doi = "10.1016/S0896-6273(00)80059-8",
language = "English (US)",
volume = "16",
pages = "415--421",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "2",

}

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

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.

UR - http://www.scopus.com/inward/record.url?scp=0029670940&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029670940&partnerID=8YFLogxK

U2 - 10.1016/S0896-6273(00)80059-8

DO - 10.1016/S0896-6273(00)80059-8

M3 - Article

C2 - 8789956

AN - SCOPUS:0029670940

VL - 16

SP - 415

EP - 421

JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 2

ER -