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Nonvesicular Release of ATP from Rat Retinal Glial (Müller) Cells is Differentially Mediated in Response to Osmotic Stress and Glutamate

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Abstract

Retinal glial (Müller) cells release ATP upon osmotic stress or activation of metabotropic glutamate receptors. ATP inhibits the osmotic Müller cell swelling by activation of P2Y1 receptors. In the present study, we determined the molecular pathways of the ATP release from Müller cells in slices of the rat retina. Administration of the ATP/ADPase apyrase induced a swelling of Müller cells under hypoosmotic conditions, and prevented the swelling-inhibitory effect of glutamate, suggesting that swelling inhibition is mediated by extracellular ATP. A hypoosmotic swelling of Müller cells was also observed in the presence of a blocker of multidrug resistance channels (MK-571), a CFTR inhibitor (glibenclamide), and connexin hemichannel blockers (18-α-glycyrrhetinic acid, 100 µM carbenoxolone). The swelling-inhibitory effect of glutamate was prevented by MK-571, the connexin hemichannel blockers, and a pannexin-1 hemichannel blocker (5 µM carbenoxolone). The p-glycoprotein blocker verapamil had no effect. As revealed by single-cell RT-PCR, subpopulations of Müller cells expressed mRNAs for pannexin-1 and -2, and connexins 30, 30.3, 32, 43, 45, and 46. The data may suggest that rat Müller cells release ATP by multidrug resistance channels, CFTR, and connexin hemichannels in response to osmotic stress, while glutamate induces a release of ATP via multidrug resistance channels, connexin hemichannels, and pannexin-1.

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Abbreviations

BAPTA/AM:

Bis-(o-aminophenoxy)ethane-N,N,N′,N’-tetra-acetic acid acetoxymethyl ester

CFTR:

Cystic fibrosis transmembrane conductance regulator

DPCPX:

8-Cyclopentyl-1,3-dipropylxanthine

LY341495:

(2S)-2-Amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid

mGluRs:

Metabotropic glutamate receptors

MK-571:

5-(3-(2-(7-Chloroquinolin-2-yl)ethenyl)phenyl)-8-dimethylcarbamyl-4,6-dithiaoctanoic acid

MRS2179:

N 6-methyl-2′-deoxyadenosine-3′,5′-bisphosphate

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Acknowledgments

This work was supported by grants from the Deutsche Forschungsgemeinschaft (GRK 1097/1; RE 849/12-2; RE 849/16-1; KO 1547/7-1).

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Informed consent was obtained from all individual participants included in the study.

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Authors and Affiliations

  1. Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany

    Juliane Voigt, Stefanie Vogler, Thomas Pannicke & Andreas Reichenbach

  2. Institute of Human Genetics, University of Regensburg, Regensburg, Germany

    Antje Grosche

  3. Department of Ophthalmology and Eye Hospital, University of Leipzig, Liebigstrasse 10-14, 04103, Leipzig, Germany

    Margrit Hollborn, Peter Wiedemann & Andreas Bringmann

  4. Helios Klinikum Aue, Aue, Germany

    Leon Kohen

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  1. Juliane Voigt
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  2. Antje Grosche
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  3. Stefanie Vogler
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  4. Thomas Pannicke
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  7. Peter Wiedemann
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  8. Andreas Reichenbach
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  9. Andreas Bringmann
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Correspondence to Andreas Bringmann.

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Voigt, J., Grosche, A., Vogler, S. et al. Nonvesicular Release of ATP from Rat Retinal Glial (Müller) Cells is Differentially Mediated in Response to Osmotic Stress and Glutamate. Neurochem Res 40, 651–660 (2015). https://doi.org/10.1007/s11064-014-1511-z

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  • DOI: https://doi.org/10.1007/s11064-014-1511-z

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