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First published online on April 12, 2007.
 Copyright © 2007 by The Physiological Society
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jphysiol.2007.127894v1
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Received January 8, 2007
Revised January 30, 2007
Accepted after revision April 10, 2007

Light triggers expression of philanthotoxin-insensitive Ca2+-permeable AMPA receptors in the developing rat retina

Ingrid K Osswald1, Alba Galan1, and Derek Bowie2*

1 McGill University, Dept Pharmacology
2 McGill University Medical School

* To whom correspondence should be addressed. E-mail: derek.bowie{at}mcgill.ca.

Ca2+-permeable AMPA receptors (AMPARs) are expressed throughout the adult CNS but yet their role in development is poorly understood. In the developing retina, most investigations have focused on Ca2+-influx through NMDARs in promoting synapse maturation and not on AMPARs. However, NMDARs are absent from many retinal cells suggesting that other Ca2+-permeable glutamate receptors may be important to consider. Here we show that inhibitory horizontal and AII amacrine cells lack NMDARs but express Ca2+-permeable AMPARs. Before eye-opening, AMPARs were fully blocked by philanthotoxin (PhTX); a selective antagonist of Ca2+-permeable AMPARs. After eye-opening, however, a subpopulation of Ca2+-permeable AMPARs were unexpectedly PhTX-resistant. Furthermore, Joro spider toxin (JSTX) and IEM-1460 also failed to antagonize demonstrating that this novel pharmacology is shared by several AMPAR channel blockers. Interestingly, PhTX-insensitive AMPARs failed to express in retinae from dark-reared animals demonstrating that light entering the eye triggers their expression. Eye-opening coincides with the consolidation of inhibitory cell connections suggesting that the developmental switch to a Ca2+-permeable AMPAR with novel pharmacology may be critical to synapse maturation in the mammalian retina.


Key words: Development • Glutamate receptor • Synaptic plasticity


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