期刊
NEUROSCIENCE
卷 158, 期 1, 页码 78-88出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2007.12.047
关键词
stargazin; AMPA receptor; glutamate receptor; NASP; CNQX; quinoxaline
资金
- Deutsche Forschungsgemeinschaft (DFG) [HO 1118/11-1]
AMPA receptors (AMPARs) mediate the majority of fast synaptic transmission in the CNS of vertebrates. They are believed to be associated with members of the transmembrane AMPA receptor regulatory protein (TARP) family. TARPs mediate the delivery of AMPA receptors to the plasma membrane and mediate their synaptic trafficking. Moreover, TARPs modulate essential electrophysiological properties of AMPA receptors. Here, we compare the influence of rat TARPs (gamma 2, gamma 3, gamma 4, and gamma 8) on pharmacological properties of rat GluR1(Q)flip. We show that agonist potencies are increased by all TARPs, but to individually different extents. On the other hand, all TARPs increase agonist potencies at the virtually non-desensitizing mutant GluRI-L479Y almost identically. Comparison of the influence of individual TARPs on relative agonist efficacies confirmed that the TARPs can be functionally subdivided into two subgroups, one consisting of gamma 2 and gamma 3 and one consisting of gamma 4 and gamma 8. Surprisingly, we found that TARPs convert certain AMPA receptor antagonists to agonists. The potency of one of these converted antagonists is dependent on the particular TARP. Moreover, TARPs (except gamma 4) reduce the ion channel block by the synthetic Joro spider toxin analog 1-naphthylacetyl spermine (NASP). In addition, TARPs increase the permeability of the receptor to calcium, indicating that TARPs directly modulate important ion pore properties. In summary, the data presented herein will illustrate and help to understand the previously unexpected complexities of modulation of AMPA receptor pharmacological properties by TARPs. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.
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