| Abstract No.: | C-B3038 |
| Country: | Canada |
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| Title: | FUNCTIONALLY DISTINCT CALCIUM-PERMEABLE AMPA RECEPTORS ARE EXPRESSED IN THE HIPPOCAMPUS AND CEREBELLUM |
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| Authors/Affiliations: | 1 David MacLean*; 1 Alba Galan; 1 Ingrid Osswald; 1 Derek Bowie;
1 McGill University, Montreal, QC, Canada
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| Content: | Traditionally, Ca2+ influx through NMDA receptors has been the focal point of investigations dealing with both development and activity dependant synaptic plasticity. However, in recent years, Ca2+ influx contributed from Ca2+ permeable AMPARs (CP-AMPARs) has become an increasingly appreciated factor in many systems such as the developing retina or interneuron synapses. Our lab has recently reported the expression and distribution of CP-AMPARs in the mammalian retina. In this study, it was found that a sub-population of these CP-AMPARs were insensitive to external polyamines (PA), the classical blocker of CP-AMPARs. Here, we extend the pharmacological profile of these novel PA-insensitive CP-AMPARs to include an insensitivity to CNQX. Paradoxically, this insensitivity is agonist-dependant, identifying a novel agonist-specific antagonism. In addition, we describe the pattern of spatial expression for both the traditional and novel forms of CP-AMPARs in the hippocampus and the cerebellum, as well as identifying calcium permeable kainate receptors in these structures. A developmental profile of receptor expression in the cerebellum is also described. Finally, we explore the molecular mechanisms of this novel pharmacology. Recombinant experiments attribute the agonist-specific antagonism by CNQX to AMPAR co-assembly with members of the transmembrane AMPAR regulatory protein (TARP) family, γ2 and γ7. We further show that TARP association attenuates internal polyamine block while accelerating the rate of external polyamine block. Thus, while the molecular composition of the novel PA-insensitive CP-AMPARs remains uncertain, our results reveal a previously unappreciated molecular heterogeneity in CP-AMPARs throughout the mammalian CNS. |
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