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Andrew T. E. Hartwick, Mélanie R. Lalonde, Steven Barnes, William H. Baldridge; Adenosine A1-Receptor Modulation of Glutamate-Induced Calcium Influx in Rat Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2004;45(10):3740-3748. doi: https://doi.org/10.1167/iovs.04-0214.
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purpose. Although adenosine receptors (A1-Rs and A2-Rs) have been identified in the mammalian retina, the role of adenosine in this tissue is not fully understood. The purpose of this work was to investigate the action of adenosine on glutamate-induced calcium influx in rat retinal ganglion cells (RGCs) and to determine whether adenosine modulates RGC voltage-gated calcium channels.
methods. Purified RGC cultures were generated from neonatal rats with a two-step panning procedure. Isolated RGCs were loaded with the ratiometric calcium-indicator dye fura-2, and the effect of adenosine (and related agonists and antagonists) on intracellular calcium levels ([Ca2+]i) during exposure to glutamate (10 μM with 10 μM glycine) was assessed. The effect of adenosine on calcium channel currents was also studied in isolated RGCs with whole-cell patch-clamp techniques. In addition, the effect of adenosine on [Ca2+]i was investigated in fura dextran-loaded RGCs in an intact adult rat retina preparation.
results. In isolated RGCs, adenosine (10 and 100 μM) significantly reduced the glutamate-induced increase in [Ca2+]i (∼30%). The effect of adenosine was blocked by the A1-R antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), but not by the A2-R antagonist 3,7-dimethyl-1-propargylxanthine (DMPX). Adenosine (10 μM) inhibited calcium channel currents by 43%, and again this effect was blocked by DPCPX, but not DMPX. Adenosine (100 μM) also significantly reduced the elevation of [Ca2+]i in RGCs in the intact retina during exposure to N-methyl-d-aspartate (NMDA; 100 μM).
conclusions. Adenosine can inhibit glutamate-induced calcium influx and voltage-gated calcium currents in rat RGCs through A1-R activation. This work supports a role for adenosine as a neuromodulator of mammalian RGCs.
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