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The Journal of Neuroscience, September 29, 2004, 24(39):8577-8583; doi:10.1523/JNEUROSCI.2812-04.2004

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Cellular/Molecular
ATP-Induced Non-Neuronal Cell Permeabilization in the Rat Inner Retina

Barbara Innocenti,^1,2 * Sylke Pfeiffer,^1 * Eberhart Zrenner,¹ Konrad Kohler,¹ and Elke Guenther^1,3

¹Laboratory of Cell Physiology and Molecular Biology, Department of Experimental Ophthalmology, University Eye Hospital, D-72076 Tuebingen, Germany, ²Department of Neurobiology and Anatomy, University of Texas Health Science Center at Houston, Houston, Texas 77030, and ³Natural and Medical Sciences Institute (NMI) at the University Tuebingen, D-72770 Reutlingen, Germany

The P2X₇ subtype holds a special position among P2X receptors because of its ability to act both as a classical, ligand-gated ion channel, and as a permeabilization pore that can induce cell death under prolonged activation by ATP.

We have shown previously that, in rat retina, P2X₇ receptors are located in the inner nuclear layer and ganglion cell layer (GCL). The present study was aimed at finding whether retinal P2X₇ receptors can act as a mediator of cell permeabilization and, if so, at identifying the cellular target(s) of this effect.

As an indicator of cell permeabilization, we used the fluorescent dye YO-PRO-1 (molecular weight, 375 Da), which enters cells only through large pores like those opened by prolonged or sustained stimulation of P2X₇ receptors and binds to DNA, providing a stable labeling of the activated cells.

Different agonists for P2 receptors were tested for their ability to cause cell permeabilization in flat-mounted rat retinas. Among them, only high concentrations of ATP (500 µM) and BzATP (2',3'-O-(4-benzoyl-benzoyl)-ATP triethylammonium) (100 µM) were able to induce accumulation of YO-PRO-1 in the GCL and in the nerve fiber layer, suggesting that different cell types were responding to P2X₇ stimulation. This effect was blocked by the P2 antagonists suramin and PPADS (pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid) and by the P2X₇-selective inhibitor Brilliant Blue G.

To identify the retinal cell types affected by ATP-induced permeabilization, we used in vivo labeling techniques. Our data clearly reveal that prolonged stimulation of P2X₇ receptors elicits permeabilization exclusively in microglial cells but not in neurons of the inner retina.

Key words: ATP; P2X₇; purinergic receptors; retinal neurotransmission; microglia; ganglion cells

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Received July 13, 2004; revised August 13, 2004; accepted August 17, 2004.

This article has been cited by other articles:

				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]

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