Dissociation between the Joro spider toxin sensitivity of recombinant a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and their ability to increase intracellular calcium

Olimpia Meucci, Richard J. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

We compared the toxin sensitivity, Ca2+ flux response and rectification properties of recombinant α-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptors obtained by transfecting human embryonic kidney (HEK) 293 cells with different ratios of GluR1 and GluR2 cDNAs (10:1 to 1:10). Simultaneous measurements of kainate-activated Ca2+ fluxes and inward currents, using fura-2 microfluorimetry under voltage clamp conditions, suggested the existence of GluR2 containing channels which are permeable to Ca2+ and insensitive to Joro spider toxin (JSTx). Imaging experiments showed that JSTx inhibition of the Ca2+ response induced by kainate was reduced by increasing the relative amount of GluR2. However, even at GluR1/GluR2(R) ratios of 1:1 and 1:4, cells were still able to flux Ca2+ when stimulated by kainate. GluR2 similarly inhibited the ability of JSTx to reduce kainate-evoked inward currents in whole cell patch-clamp experiments. Variations in the rectification properties of the AMPA currents, induced by changes in the cDNA ratio, were not always correlated with the changes in toxin sensitivity and [Ca2+](i) response. Thus, cells with almost linear I-V relationships were partially blocked by JSTx and still Ca2+ permeable. Our results indicate a dissociation between the toxin sensitivity and Ca2+ flux through GluR2 containing AMPA receptors and suggest that receptors with diverse Ca2+ permeabilities are generated by the expression of variable amounts of GluR2. Copyright (C) 1998 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)1431-1443
Number of pages13
JournalNeuropharmacology
Volume37
Issue number10-11
DOIs
StatePublished - Oct 1 1998

Keywords

  • AMPA receptors
  • Ca permeability
  • Joro spider toxin
  • Toxin sensitivity

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

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