Light triggers expression of philanthotoxin‐insensitive Ca 2 +‐permeable AMPA receptors in the developing rat retina

Ca 2 +‐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 Ca 2+ influx through NMDARs in promoting synapse maturation and not on AMPARs. However, NMDARs are absent from many retinal cells suggesting that other Ca 2+ ‐permeable glutamate receptors may be important to consider. Here we show that inhibitory horizontal and AII amacrine cells lack NMDARs but express Ca 2+ ‐permeable AMPARs. Before eye‐opening, AMPARs were fully blocked by philanthotoxin (PhTX), a selective antagonist of Ca 2+ ‐permeable AMPARs. After eye‐opening, however, a subpopulation of Ca 2+ ‐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 Ca 2+ ‐permeable AMPAR with novel pharmacology may be critical to synapse maturation in the mammalian retina.