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Salvatore L. Stella, Jr., Nicholas Dale, Jean Sevigny; Light, Adenosine Transporters, And Ecto-nucleotidases Contribute To Adenosine Levels In The Outer Retina. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4115.
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Previous work in our laboratory has shown that endogenous adenosine levels suppress transmitter release from photoreceptors. Interestingly, adenosine levels are influenced by conditions of illumination as well as by adenosine transporters. However, it is not known how adenosine levels are regulated in the outer retina. The goal of this study was to investigate the effect of light, adenosine transporters, and the distribution of enzymes involved in the regulation of adenosine in the outer retina.
Experiments were performed in preparations from mice and larval tiger salamanders. [Ca2+]i levels were measured from photoreceptors using either fura-2/AM or fluo-4/AM. Whole cell patch-clamp recordings were used to measure photoreceptor calcium currents (ICa) and light-evoked currents in second-order neurons to assess transmitter release. Adenosine measurements were made using adenosine biosensors with a potentiostat. Antibodies to nucleoside triphosphate diphosphohydrolase-1 (NTPDase1), -2, and -3 were used to map the localization of purine metabolism in the outer retina.
Light stimulation suppressed endogenous adenosine levels in dark-adapted retina, which partially recovered. Low levels of adenosine release could be detected with elevated K+, however stimulation with glutamate receptor agonists (AMPA/Kainate) showed no significant change in basal adenosine levels. Adenosine release was partially decreased following the removal of extracellular Ca2+, implying some Ca2+-dependent release. Adenosine transport blockers caused an increase in extracellular adenosine, suppressed synaptic transmission onto second-order neurons, and inhibited photoreceptor voltage-dependent Ca2+ influx, suggesting that adenosine transporters remove adenosine from the synapse. Ecto-nucleotidases (NTPDase 1 and NTPDase 2) were highly expressed at photoreceptors terminals.
Our findings indicate that adenosine levels are tightly regulated by conditions of illumination and ecto-nucleotidases in and around photoreceptor terminals. These findings highlight the important and dynamic light-modulated nature of adenosine on transmitter release in the retina and provide a novel way to regulate both the excitability and tonic release of L-glutamate from photoreceptors.
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