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Enhanced functional detection of synaptic calcium-permeable AMPA receptors using intracellular NASPM

Coombs, Ian D; Bats, Cécile; Sexton, Craig A; Studniarczyk, Dorota; Cull-Candy, Stuart G; Farrant, Mark; (2023) Enhanced functional detection of synaptic calcium-permeable AMPA receptors using intracellular NASPM. eLife , 12 , Article e66765. 10.7554/eLife.66765. Green open access

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Abstract

Calcium-permeable AMPA-type glutamate receptors (CP-AMPARs) contribute to many forms of synaptic plasticity and pathology. They can be distinguished from GluA2-containing calcium-impermeable AMPARs by the inward rectification of their currents, which reflects voltage-dependent channel block by intracellular spermine. However, the efficacy of this weakly permeant blocker is differentially altered by the presence of AMPAR auxiliary subunits - including transmembrane AMPAR regulatory proteins, cornichons and GSG1L - which are widely expressed in neurons and glia. This complicates the interpretation of rectification as a measure of CP-AMPAR expression. Here we show that inclusion of the spider toxin analogue 1‑naphthylacetyl spermine (NASPM) in the intracellular solution results in complete block of GluA1-mediated outward currents irrespective of the type of associated auxiliary subunit. In neurons from GluA2-knockout mice expressing only CP-AMPARs, intracellular NASPM, unlike spermine, completely blocks outward synaptic currents. Thus, our results identify a functional measure of CP-AMPARs, that is unaffected by their auxiliary subunit content.

Type: Article
Title: Enhanced functional detection of synaptic calcium-permeable AMPA receptors using intracellular NASPM
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.7554/eLife.66765
Publisher version: http://doi.org/10.7554/eLife.66765
Language: English
Additional information: Copyright © Coombs et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/10169887
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