Article abstract

Nature Neuroscience 10, 1260 - 1267 (2007)
Published online: 16 September 2007 | Corrected online: 23 October 2007 | doi:10.1038/nn1966



There is a Corrigendum (December 2007) associated with this Article.

Stargazin attenuates intracellular polyamine block of calcium-permeable AMPA receptors

David Soto1, Ian D Coombs1, Leah Kelly1, Mark Farrant1 & Stuart G Cull-Candy1

Endogenous polyamines profoundly affect the activity of various ion channels, including that of calcium-permeable AMPA-type glutamate receptors (CP-AMPARs). Here we show that stargazin, a transmembrane AMPAR regulatory protein (TARP) known to influence transport, gating and desensitization of AMPARs, greatly reduces block of CP-AMPARs by intracellular polyamines. By decreasing CP-AMPAR affinity for cytoplasmic polyamines, stargazin enhances the charge transfer following single glutamate applications and eliminates the frequency-dependent facilitation seen with repeated applications. In cerebellar stellate cells, which express both synaptic CP-AMPARs and stargazin, we found that the rectification and unitary conductance of channels underlying excitatory postsynaptic currents were matched by those of recombinant AMPARs only when the latter were associated with stargazin. Taken together, our observations establish modulatory actions of stargazin that are specific to CP-AMPARs, and suggest that during synaptic transmission the activity of such receptors, and thus calcium influx, is fundamentally changed by TARPs.

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  1. Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.

Correspondence to: Stuart G Cull-Candy1 e-mail: s.cull-candy@ucl.ac.uk

Correspondence to: Mark Farrant1 e-mail: m.farrant@ucl.ac.uk

* In the version of this article initially published, the filled and open symbols were switched in Figure 3b. A minus sign was also introduced into the text describing the figure. The figure has been corrected, and the sentence in the text beneath the figure should read: "By plotting conductance against voltage35, it can be seen that stargazin induced a +33 mV shift in the voltage for half-maximal block by spermine (Fig.3b)." The error has been corrected in the HTML and PDF versions of the article.

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