Light triggers expression of philanthotoxin-insensitive Ca2+-permeable AMPA receptors in the developing rat retina.
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.
Osswald
Ingrid K
IK
Department of Pharmacology & Therapeutics, McIntyre Medical Sciences Building, Room 1317, McGill University, Montreal, Québec, Canada H3A 1Y6.
Galan
Alba
A
Bowie
Derek
D
D000221:Adaptation, Ocular; D000375:Aging / Q000378:metabolism; D025042:Amacrine Cells / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism / Q000528:radiation effects*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D003623:Dark Adaptation; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008027:Light; D008297:Male; D008564:Membrane Potentials / Q000528:radiation effects; D009433:Neural Inhibition / Q000528:radiation effects; D010636:Phenols / Q000494:pharmacology*; D011073:Polyamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D012160:Retina / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism / Q000528:radiation effects*; D051248:Retinal Horizontal Cells / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism / Q000528:radiation effects*; D013569:Synapses / Q000378:metabolism / Q000528:radiation effects; D009435:Synaptic Transmission / Q000528:radiation effects; D014795:Visual Pathways / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism / Q000528:radiation effects*
D010636:Phenols; D011073:Polyamines; D018091:Receptors, AMPA; C074003:philanthotoxin 343; D002118:Calcium