Evidence for the involvement of purinergic P2X receptors in outer retinal processing.
Extracellular ATP mediates fast excitatory neurotransmission in many regions of the central nervous system through activation of P2X receptors. Although several P2X receptor subunits have been identified in the mammalian retina, little is known about the functional role of these receptors in retinal signalling. The purpose of the present study was to investigate whether purinergic P2X(7) receptors are involved in outer retinal processing by assessing receptor localization, degradation of extracellular ATP and the effect of functional activation of P2X(7) receptors on the electroretinogram (ERG). Using light and electron microscopy, we demonstrated that P2X(7) receptors are expressed postsynaptically on horizontal cell processes as well as presynaptically on photoreceptor synaptic terminals in both the rat and marmoset retina. Using an enzyme cytochemical method, we showed that ecto-ATPases are active in the outer plexiform layer of the rat retina, providing a mechanism by which purinergic synaptic transmission can be rapidly terminated. Finally, we evaluated the role of P2X(7) receptors in retinal function by assessing changes to the ERG response of rats after intravitreal delivery of the P2X(7) receptor agonist benzoyl benzoyl ATP (BzATP). Intravitreal injection of BzATP resulted in a sustained increase (up to 58%) in the amplitude of the photoreceptor-derived a-wave of the ERG. In contrast, BzATP caused a transient reduction in the rod- and cone-derived postreceptoral responses. These results provide three lines of evidence for the involvement of extracellular purines in outer retinal processing.
Puthussery
Theresa
T
Department of Anatomy and Cell Biology, The University of Melbourne, Parkville 3010 Victoria, Australia.
Yee
Peter
P
Vingrys
Algis J
AJ
Fletcher
Erica L
EL
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002144:Callithrix; D004596:Electroretinography; D005110:Extracellular Space / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D016253:Microscopy, Immunoelectron; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000096:biosynthesis / Q000502:physiology*; D058486:Receptors, Purinergic P2X7; D012160:Retina / Q000378:metabolism / Q000502:physiology*; D013045:Species Specificity; D009435:Synaptic Transmission
C546470:P2rx7 protein, rat; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; C027201:ectoATPase