Stargazin attenuates intracellular polyamine block of calcium-permeable AMPA receptors

被引：156

作者：

Soto, David ^{[1
]}

Coombs, Ian D. ^{[1
]}

Kelly, Leah ^{[1
]}

Farrant, Mark ^{[1
]}

Cull-Candy, Stuart G. ^{[1
]}

机构：

[1] UCL, Dept Pharmacol, London WC1E 6BT, England

来源：

NATURE NEUROSCIENCE | 2007年 / 10卷 / 10期

基金：

英国惠康基金;

关键词：

D O I：

10.1038/nn1966

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：1260 / 1267

页数：8

共 51 条

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