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Neuron 2009 Jan 15;611:101-12. doi: 10.1016/j.neuron.2008.11.009.
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Autoinactivation of neuronal AMPA receptors via glutamate-regulated TARP interaction.

Morimoto-Tomita M , Zhang W , Straub C , Cho CH , Kim KS , Howe JR , Tomita S .

Neuronal AMPA receptors autoinactivate at high concentrations of glutamate, i.e., the current declines at glutamate concentrations above 10-100 microM. The mechanisms underlying this phenomenon are unclear. Stargazin-like TARPs are AMPA receptor auxiliary subunits that modulate receptor trafficking and channel properties. Here, we found that neuronal AMPA receptors and recombinant AMPA receptors coexpressed with stargazin autoinactivate at high concentrations of glutamate, whereas recombinant AMPA receptors expressed alone do not. The reduction of currents at high glutamate concentrations is not associated with a reduction of AMPA receptor number, but rather with the loss of stargazin-associated allosteric modulation of channel gating. We show that receptor desensitization promotes the dissociation of TARP-AMPA receptor complexes in a few milliseconds. This dissociation mechanism contributes to synaptic short-term modulation. The results demonstrate a mechanism for dynamic regulation of AMPA receptor activity to tune synaptic strength.

PubMed ID: 19146816
PMC ID: PMC2649795
Article link: Neuron
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: cacng2

References [+] :
Armstrong, Measurement of conformational changes accompanying desensitization in an ionotropic glutamate receptor. 2006, Pubmed, Xenbase