HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Hartwick, A. T. E. Articles by Baldridge, W. H. Search for Related Content PubMed PubMed Citation Articles by Hartwick, A. T. E. Articles by Baldridge, W. H.

Adenosine A₁-Receptor Modulation of Glutamate-Induced Calcium Influx in Rat Retinal Ganglion Cells

¹From the Retina and Optic Nerve Research Laboratory and the ²Departments of Anatomy and Neurobiology, ³Physiology and Biophysics, and ⁴Ophthalmology and Visual Sciences, Dalhousie University, Halifax, Nova Scotia, Canada.

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.

This article has been cited by other articles:

				J. A. Murphy, A. T. E. Hartwick, U. Rutishauser, and D. B. Clarke Endogenous Polysialylated Neural Cell Adhesion Molecule Enhances the Survival of Retinal Ganglion Cells Invest. Ophthalmol. Vis. Sci., February 1, 2009; 50(2): 861 - 869. [Abstract] [Full Text] [PDF]

				A. T. E. Hartwick, C. M. Hamilton, and W. H. Baldridge Glutamatergic calcium dynamics and deregulation of rat retinal ganglion cells J. Physiol., July 15, 2008; 586(14): 3425 - 3446. [Abstract] [Full Text] [PDF]

				A. T. E. Hartwick, J. R. Bramley, J. Yu, K. T. Stevens, C. N. Allen, W. H. Baldridge, P. J. Sollars, and G. E. Pickard Light-Evoked Calcium Responses of Isolated Melanopsin-Expressing Retinal Ganglion Cells J. Neurosci., December 5, 2007; 27(49): 13468 - 13480. [Abstract] [Full Text] [PDF]

				X. Zhang, M. Zhang, A. M. Laties, and C. H. Mitchell Stimulation of P2X7 Receptors Elevates Ca2+ and Kills Retinal Ganglion Cells Invest. Ophthalmol. Vis. Sci., June 1, 2005; 46(6): 2183 - 2191. [Abstract] [Full Text] [PDF]