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

Indira M. Raman; Gang Tong; Craig E. Jahr

doi:10.1016/S0896-6273(00)80059-8

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

Indira M. Raman, Gang Tong^*, Craig E. Jahr

^*Corresponding author for this work

Neurobiology

Research output: Contribution to journal › Article › peer-review

261 Scopus citations

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 language	English (US)
Pages (from-to)	415-421
Number of pages	7
Journal	Neuron
Volume	16
Issue number	2
DOIs	https://doi.org/10.1016/S0896-6273(00)80059-8
State	Published - Feb 1996

Funding

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.).

ASJC Scopus subject areas

General Neuroscience

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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 Jahr, {Craig E.}",

note = "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.). ",

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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.).

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

Abstract

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ASJC Scopus subject areas

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