title: P2X7R modulation of visually evoked synaptic responses in the retina.
abstract: P2X7Rs are distributed throughout all layers of the retina, and thus, their localisation on various cell types puts into question their specific site(s) of action. Using a dark-adapted, ex vivo mouse retinal whole mount preparation, the present study aimed to characterise the effect of P2X7R activation on light-evoked, excitatory RGC ON-field excitatory post-synaptic potentials (fEPSPs) and on outer retinal electroretinogram (ERG) responses under comparable conditions. The pharmacologically isolated NMDA receptor-mediated RGC ON-fEPSP was reduced in the presence of BzATP, an effect which was significantly attenuated by A438079 and other selective P2X7R antagonists A804598 or AF27139. In physiological Krebs medium, BzATP induced a significant potentiation of the ERG a-wave, with a concomitant reduction in the b-wave and the power of the oscillatory potentials. Conversely, in the pharmacologically modified Mg2+-free perfusate, BzATP reduced both the a-wave and b-wave. The effects of BzATP on the ERG components were suppressed by A438079. A role for P2X7R function in visual processing in both the inner and outer retina under physiological conditions remains controversial. The ON-fEPSP was significantly reduced in the presence of A804598 but not by A438079 or AF27139. Furthermore, A438079 did not have any effect on the ERG components in physiological Krebs but potentiated and reduced the a-wave and b-wave, respectively, when applied to the pharmacologically modified medium. Therefore, activation of P2X7Rs affects the function in the retinal ON pathway. The presence of a high concentration of extracellular ATP would most likely contribute to the modulation of visual transmission in the retina in the pathophysiological microenvironment.
authors.affiliation: Visual Neuroscience, UCL Institute of Ophthalmology, London, EC1V 9EL, UK.
authors.forename: Seetal
authors.initials: S
authors.lastname: Chavda
authors.affiliation: Ocular Biology and Therapeutics, UCL Institute of Ophthalmology, London, EC1V 9EL, UK.|NIHR Biomedical Research Centre in Ophthalmology, London, EC1V 9EL, UK.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Luthert
authors.affiliation: Visual Neuroscience, UCL Institute of Ophthalmology, London, EC1V 9EL, UK. T.Salt@ucl.ac.uk.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Salt
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004596:Electroretinography; D005074:Evoked Potentials, Visual / Q000187:drug effects* / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D006146:Guanidines / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D010775:Photic Stimulation; D058911:Purinergic P2X Receptor Agonists / Q000494:pharmacology; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D012160:Retina / Q000187:drug effects* / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: C539459:2-cyano-1-((1S)-1-phenylethyl)-3-quinolin-5-ylguanidine; C523668:3-(5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl)methylpyridine; D006146:Guanidines; D058911:Purinergic P2X Receptor Agonists; D058920:Purinergic P2X Receptor Antagonists; D011725:Pyridines; D011804:Quinolines; D058486:Receptors, Purinergic P2X7; D013777:Tetrazoles; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate
keywords: Adenosine 5′-triphosphate; Neuromodulation; P2X7 receptor; Retina