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Cited by 842Neuroscience and Neuropharmacology ResearchNicotinic Acetylcholine Receptors StudyIon channel regulation and function

Ca 2+ /calmodulin-kinase II enhances channel conductance of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate type glutamate receptors

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Derkach, Victor, Barria, Andres, Soderling, Thomas R.·1999·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.96.6.3269PMC PMC15931
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Abstract

The ability of central glutamatergic synapses to change their strength in response to the intensity of synaptic input, which occurs, for example, in long-term potentiation (LTP), is thought to provide a cellular basis for memory formation and learning. LTP in the CA1 field of the hippocampus requires activation of Ca2+/calmodulin-kinase II (CaM-KII), which phosphorylates Ser-831 in the GluR1 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate glutamate receptor (AMPA-R), and this activation/phosphorylation is thought to be a postsynaptic mechanism in LTP. In this study, we have identified a molecular mechanism by which CaM-KII potentiates AMPA-Rs. Coexpression in HEK-293 cells of activated CaM-KII with GluR1 did not affect the glutamate affinity of the receptor, the kinetics of desensitization and recovery, channel rectification, open probability, or gating. Single-channel recordings identified multiple conductance states for GluR1, and coexpression with CaM-KII or a mutation of Ser-831 to Asp increased the contribution of the higher conductance states. These results indicate that CaM-KII can mediate plasticity at glutamatergic synapses by increasing single-channel conductance of existing functional AMPA-Rs or by recruiting new high-conductance-state AMPA-Rs.

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  • CaMKII activation leads to the phosphorylation of a number of proteins including AMPARs themselves.

    “This leads to the phosphorylation of a number of proteins including AMPARs themselves (Derkach et al. 1999).”

    From NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD). (2012) · cites this paper as Derkach et al. 1999

    The Results report that activated CaMKII greatly enhances phosphorylation of the AMPAR subunit GluR1 at Ser-831, and the Discussion identifies CaMKII-mediated phosphorylation of AMPARs. These passages support the AMPAR part of the claim, but do not establish that CaMKII phosphorylates a number of other proteins. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • NMDAR-dependent LTP requires Ca2+ influx leading to activation of CaMKII/PKC which directly phosphorylate GluA1 S831, increasing GluA1 single channel conductance and promoting GluA1 targeting to the PSD.

    “NMDAR-dependent LTP requires Ca2+ influx leading to activation of CaMKII/PKC which directly phosphorylate GluA1 S831, increasing GluA1 single channel conductance and promoting GluA1 targeting to the PSD (Mammen et al., 1997, Barria et al., 1997a, Derkach et al., 1999, Kristensen et al., 2011, Barria et al., 1997b).”

    From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Derkach et al., 1999

    The Abstract and Results report that CaMKII phosphorylation of GluR1 (GluA1) at Ser-831 increases the contribution of higher single-channel conductance states. The paper also says PKC phosphorylates Ser-831, but treats its effect on conductance as presumptive. It does not establish NMDAR dependence or show that this phosphorylation promotes GluA1 targeting to the postsynaptic density. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Phosphorylation of S831 of heterologously expressed GluA1 by CaMKII increases single-channel conductance.

    “Phosphorylation of S831 of heterologously expressed GluA1 by CaMKII increases single-channel conductance (267, 268).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [267]

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Cited by

Sorted by citations

Authors
Derkach, V., Barria, A., & Soderling, T. R.
Affiliations
  • Oregon Health & Science University (US)
  • Vollum Institute, Oregon Health Sciences University, Portland, OR 97201
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1999-03-16
Volume
96
Issue
6
Pages
3269-3274
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.96.6.3269
PMC
PMC15931
OpenAlex
W1983252720
Cited by
842
References
1
Citations by year
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FWCI
12.41
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R01NS027037, NS 27037)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Keywords
AMPA receptors, GluR1, long-term potentiation, synaptic plasticity, single-channel conductance, high-conductance state, glutamatergic synapses, hippocampal CA1, receptor desensitization, postsynaptic plasticity
MeSH terms
Cell Line, Humans, Ion Channels, Neuronal Plasticity, Phosphorylation, Signal Transduction, Long-Term Potentiation, Calcium-Calmodulin-Dependent Protein Kinases, Receptors, AMPA, Calcium-Calmodulin-Dependent Protein Kinase Type 2

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