Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/32589
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Título : Molecular Mechanism of AMPA Receptor Noncompetitive Antagonism
Autor : Balannik, Victoria, Menniti, Frank S., Paternain, Ana V., Lerma Gómez, Juan, Stern-Bach, Yael
Fecha de publicación : 20-Oct-2005
Editor: Elsevier
Resumen: AMPA-type glutamate receptors are specifically inhibited by the noncompetitive antagonists GYKI-53655 and CP-465,022, which act through sites and mechanisms that are not understood. Using receptor mutagenesis, we found that these antagonists bind at the interface between the S1 and S2 glutamate binding core and channel transmembrane domains, specifically interacting with S1-M1 and S2-M4 linkers, thereby disrupting the transduction of agonist binding into channel opening. We also found that the antagonists' affinity is higher for agonist-unbound receptors than for activated nondesensitized receptors, further depending on the level of S1 and S2 domain closure. These results provide evidence for substantial conformational changes in the S1-M1 and S2-M4 linkers following agonist binding and channel opening, offering a conceptual frame to account for noncompetitive antagonism of AMPA receptors.
Descripción : 10 páginas, 6 figuras.
Versión del editor: http://dx.doi.org/10.1016/j.neuron.2005.09.024
URI : http://hdl.handle.net/10261/32589
ISSN: 0896-6273
DOI: 10.1016/j.neuron.2005.09.024
Citación : Neuron 48(2): 279-288 (2005)
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