Journal
ELIFE
Volume 12, Issue -, Pages -Publisher
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.66765
Keywords
AMPA-type glutamate receptor; excitatory postsynaptic current; TARP; spermine; NASPM; rectification; Mouse
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Calcium-permeable AMPA-type glutamate receptors (CP-AMPARs) play important roles in synaptic plasticity and pathology. The presence of auxiliary subunits complicates the interpretation of current rectification as a measure of CP-AMPAR expression. However, the inclusion of the spider toxin analog 1-naphthylacetyl spermine (NASPM) in the intracellular solution can block GluA1-mediated outward currents regardless of the auxiliary subunit type, providing a functional measure of CP-AMPARs.
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 the inclusion of the spider toxin analog 1-naphthylacetyl spermine (NASPM) in the intracellular solution results in a 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.
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