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

• Published in: The Journal of physiology 2007-07, Vol.582 (1), p.95-111
• Main Authors: Osswald, Ingrid K., Galan, Alba, Bowie, Derek
• Format: Article
• Language: English
• Subjects: Adaptation, Ocular; Aging - metabolism; Amacrine Cells - drug effects; Amacrine Cells - growth & development; Amacrine Cells - metabolism; Amacrine Cells - radiation effects; Animals; Animals, Newborn; Calcium - metabolism; Dark Adaptation; Female; In Vitro Techniques; Kinetics; Light; Male; Membrane Potentials - radiation effects; Neural Inhibition - radiation effects; Neuroscience; Phenols - pharmacology; Polyamines - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, AMPA - drug effects; Receptors, AMPA - metabolism; Receptors, AMPA - radiation effects; Retina - drug effects; Retina - growth & development; Retina - metabolism; Retina - radiation effects; Retinal Horizontal Cells - drug effects; Retinal Horizontal Cells - growth & development; Retinal Horizontal Cells - metabolism; Retinal Horizontal Cells - radiation effects; Synapses - metabolism; Synapses - radiation effects; Synaptic Transmission - radiation effects; Visual Pathways - drug effects; Visual Pathways - growth & development; Visual Pathways - metabolism; Visual Pathways - radiation effects
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2007.127894

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.