Potently and selectively blocks the desensitization of ionotropic glutamate AMPA receptor (GRIA1, GRIA2, GRIA3 and GRIA4). Can also open already desensitized GRIA1 receptors. Binds to a different site than does the drug cyclothiazide . The toxin acts like a straightjacket on the ligand-binding domain (LBD) "gating ring" of the receptor, restraining the domains via both intra- and interdimer cross-links such that agonist-induced closure of the LBD "clamshells" is transduced into an irislike expansion of the gating ring . Application of the toxin to hippocampal slices causes a large and rapid increase in resting AMPAR-mediated current leading to neuronal death .
A novel Conus snail polypeptide causes excitotoxicity by blocking desensitization of AMPA receptors.Walker C.S., Jensen S., Ellison M., Matta J.A., Lee W.Y., Imperial J.S., Duclos N., Brockie P.J., Madsen D.M., Isaac J.T., Olivera B., Maricq A.V.Curr. Biol. 19:900-908(2009)
Research Topic:Others
