Hippocampal AMPA Receptor Gating Controlled by Both TARP and Cornichon Proteins.
Summary of "Hippocampal AMPA Receptor Gating Controlled by Both TARP and Cornichon Proteins."
Transmembrane AMPA receptor regulatory proteins (TARPs) and cornichon proteins (CNIH-2/3) independently modulate AMPA receptor trafficking and gating. However, the potential for interactions of these subunits within an AMPA receptor complex is unknown. Here, we find that TARPs γ-4, γ-7, and γ-8, but not γ-2, γ-3, or γ-5, cause AMPA receptors to "resensitize" upon continued glutamate application. With γ-8, resensitization occurs with all GluA subunit combinations; however, γ-8-containing hippocampal neurons do not display resensitization. In recombinant systems, CNIH-2 abrogates γ-8-mediated resensitization and modifies AMPA receptor pharmacology and gating to match that of hippocampal neurons. In hippocampus, γ-8 and CNIH-2 associate in postsynaptic densities and CNIH-2 protein levels are markedly diminished in γ-8 knockout mice. Manipulating neuronal CNIH-2 levels modulates the electrophysiological properties of extrasynaptic and synaptic γ-8-containing AMPA receptors. Thus, γ-8 and CNIH-2 functionally interact with common hippocampal AMPA receptor complexes to modulate synergistically kinetics and pharmacology.
Affiliation
Department of Neuroscience, Eli Lilly and Company, Indianapolis, IN 46285, USA.
Journal Details
This article was published in the following journal.
Name: Neuron
ISSN: 1097-4199
Pages: 1082-96
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21172611
- DOI: http://dx.doi.org/10.1016/j.neuron.2010.11.026
Medical and Biotech [MESH] Definitions
Receptors, Ampa
Cell surface proteins that bind glutamate and directly gate ion channels in cell membranes. AMPA receptors were originally discriminated from other glutamate receptors by their affinity for the agonist AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid). They are probably the most common mediators of fast excitatory synaptic transmission in the central nervous system. Several subtypes have been cloned, and for some types the traditional distinction from kainate receptors may not apply.
Sensory Gating
The ability of the BRAIN to suppress neuronal responses to external sensory inputs, such as auditory and visual stimuli. Sensory filtering (or gating) allows humans to block out irrelevant, meaningless, or redundant stimuli.
Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
An IBOTENIC ACID homolog and glutamate agonist. The compound is the defining agonist for the AMPA subtype of glutamate receptors (RECEPTORS, AMPA). It has been used as a radionuclide imaging agent but is more commonly used as an experimental tool in cell biological studies.
Ion Channel Gating
The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.
Hippocampus
A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle. The hippocampus, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.
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