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Stargazin attenuates intracellular polyamine block of calcium-permeable AMPA receptors

A Corrigendum to this article was published on 01 December 2007

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Abstract

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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Figure 1: Stargazin modifies the I-V relationship of recombinant Ca2+-permeable AMPAR channels.
Figure 2: Stargazin alters conductance but not Ca2+ permeability of AMPARs.
Figure 3: Effect of stargazin on polyamine block and deactivation of GluR4 AMPARs.
Figure 4: Stargazin alters the time course of spermine block and eliminates frequency-dependent facilitation of Ca2+-permeable GluR4 AMPARs.
Figure 5: Rectification and conductance properties of synaptic AMPARs are consistent with the presence of stargazin.
Figure 6: Stargazin does not affect rectification of GluR4 in the absence of polyamines.
Figure 7: Stargazin reduces the apparent affinity of GluR4 receptors for spermine.
Figure 8: Stargazin modifies spermidine block of GluR4 receptors.

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Change history

  • 23 October 2007

    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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Acknowledgements

We thank B. Clark for help; R. Nicoll (University of California San Francisco) for providing TARP DNAs; and I. Mody (University of California Los Angeles) for EVAN software. This work was supported by a Wellcome Trust Programme Grant (to S.G.C.-C. and M.F.) and the Royal Society. L.K. was supported by a Wellcome Trust Studentship during part of this work, and S.G.C.-C. holds a Royal Society-Wolfson Research Award.

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Correspondence to Mark Farrant or Stuart G Cull-Candy.

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Soto, D., Coombs, I., Kelly, L. et al. Stargazin attenuates intracellular polyamine block of calcium-permeable AMPA receptors. Nat Neurosci 10, 1260–1267 (2007). https://doi.org/10.1038/nn1966

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