Journal article
Autoinactivation of Neuronal AMPA Receptors via Glutamate-Regulated TARP Interaction
Neuron (Cambridge, Mass.), Vol.61(1), pp.101-112
2009
DOI: 10.1016/j.neuron.2008.11.009
PMID: 19146816
Abstract
Neuronal AMPA receptors autoinactivate at high concentrations of glutamate, i.e., the current declines at glutamate concentrations above 10–100 μM. The mechanisms underlying this phenomenon are unclear. Stargazin-like TARPs are AMPA receptor auxiliary subunits that modulate receptor trafficking and channel properties. Here, we found that neuronal AMPA receptors and recombinant AMPA receptors coexpressed with stargazin autoinactivate at high concentrations of glutamate, whereas recombinant AMPA receptors expressed alone do not. The reduction of currents at high glutamate concentrations is not associated with a reduction of AMPA receptor number, but rather with the loss of stargazin-associated allosteric modulation of channel gating. We show that receptor desensitization promotes the dissociation of TARP-AMPA receptor complexes in a few milliseconds. This dissociation mechanism contributes to synaptic short-term modulation. The results demonstrate a mechanism for dynamic regulation of AMPA receptor activity to tune synaptic strength.
Details
- Title: Subtitle
- Autoinactivation of Neuronal AMPA Receptors via Glutamate-Regulated TARP Interaction
- Creators
- Megumi Morimoto-Tomita - Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520, USAWei Zhang - Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USAChristoph Straub - Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520, USAChang-Hoon Cho - Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USAKwang S Kim - Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520, USAJames R Howe - Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USASusumu Tomita - Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520, USA
- Resource Type
- Journal article
- Publication Details
- Neuron (Cambridge, Mass.), Vol.61(1), pp.101-112
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.neuron.2008.11.009
- PMID
- 19146816
- ISSN
- 0896-6273
- eISSN
- 1097-4199
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: NS047712, NS057725; DOI: 10.13039/100001207, name: Esther A. and Joseph Klingenstein Fund
- Language
- English
- Date published
- 2009
- Academic Unit
- Surgery
- Record Identifier
- 9984051722902771
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