Protein kinase A regulates calcium permeability of NMDA receptors

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

212 Scopus Citations
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Author(s)

  • V. Arvydas Skeberdis
  • Vivien Chevaleyre
  • Jesse H. Goldberg
  • Diana L. Pettit
  • Sylvia O. Suadicani
  • Ying Lin
  • Michael V. L. Bennett
  • Rafael Yuste
  • Pablo E. Castillo
  • R. Suzanne Zukin

Detail(s)

Original languageEnglish
Pages (from-to)501-510
Journal / PublicationNature Neuroscience
Volume9
Issue number4
Publication statusPublished - Apr 2006
Externally publishedYes

Abstract

Calcium (Ca2+) influx through NMDA receptors (NMDARs) is essential for synaptogenesis, experience-dependent synaptic remodeling and plasticity. The NMDAR-mediated rise in postsynaptic Ca2+ activates a network of kinases and phosphatases that promote persistent changes in synaptic strength, such as long-term potentiation (LTP). Here we show that the Ca 2+ permeability of neuronal NMDARs is under the control of the cyclic AMP-protein kinase A (cAMP-PKA) signaling cascade. PKA blockers reduced the relative fractional Ca2+ influx through NMDARs as determined by reversal potential shift analysis and by a combination of electrical recording and Ca2+ influx measurements in rat hippocampal neurons in culture and hippocampal slices from mice. In slices, PKA blockers markedly inhibited NMDAR-mediated Ca2+ rises in activated dendritic spines, with no significant effect on synaptic current. Consistent with this, PKA blockers depressed the early phase of NMDAR-dependent LTP at hippocampal Schaffer collateral-CA1 (Sch-CA1) synapses. Our data link PKA-dependent synaptic plasticity to Ca2+ signaling in spines and thus provide a new mechanism whereby PKA regulates the induction of LTP. © 2006 Nature Publishing Group.

Citation Format(s)

Protein kinase A regulates calcium permeability of NMDA receptors. / Skeberdis, V. Arvydas; Chevaleyre, Vivien; Lau, C. Geoffrey; Goldberg, Jesse H.; Pettit, Diana L.; Suadicani, Sylvia O.; Lin, Ying; Bennett, Michael V. L.; Yuste, Rafael; Castillo, Pablo E.; Zukin, R. Suzanne.

In: Nature Neuroscience, Vol. 9, No. 4, 04.2006, p. 501-510.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal