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The Journal of Neuroscience, August 15, 2000, 20(16):5965-5972
P2X7 Receptors in Müller Glial Cells from the
Human Retina
Thomas
Pannicke1,
Wolfgang
Fischer2,
Bernd
Biedermann1,
Hiltrud
Schädlich2,
Jens
Grosche1,
Frank
Faude3,
Peter
Wiedemann3,
Clemens
Allgaier2,
Peter
Illes2,
Geoffrey
Burnstock4, and
Andreas
Reichenbach1
1 Paul-Flechsig-Institute for Brain Research,
University of Leipzig, 04109 Leipzig, Germany,
2 Rudolf-Boehm-Institute of Pharmacology and Toxicology,
University of Leipzig, 04103 Leipzig, Germany, 3 Department
of Ophthalmology, University of Leipzig, 04103 Leipzig, Germany,
and 4 Autonomic Neuroscience Institute, Rowland Hill
Street, London NW3 2PF, United Kingdom
ATP has been shown to be an important extracellular signaling
molecule. There are two subgroups of receptors for ATP (and other
purines and pyrimidines): the ionotropic P2X and the G-protein-coupled P2Y receptors. Different subtypes of these receptors have been identified by molecular biology, but little is known about their functional properties in the nervous system. Here we present data for
the existence of P2 receptors in Müller (glial) cells of the
human retina. The cells were studied by immunocytochemistry, electrophysiology, Ca2+-microfluorimetry, and
molecular biology. They displayed both P2Y and P2X receptors. Freshly
enzymatically isolated cells were used throughout the study. Although
the [Ca2+]i response to ATP was
dominated by release from intracellular stores, there is multiple
evidence that the ATP-induced membrane currents were caused by an
activation of P2X7 receptors. Immunocytochemistry and
single-cell RT-PCR revealed the expression of P2X7
receptors by Müller cells. In patch-clamp studies, we found that
(1) benzoyl-benzoyl ATP (BzATP) was the most effective agonist to evoke
large inward currents and (2) the currents were abolished by P2X
antagonists; however, (3) long-lasting application of BzATP did not
cause an opening of large pores in addition to the cationic channels.
By microfluorimetry it was shown that the P2X receptors mediated a
Ca2+ influx that contributed a small component to
the total [Ca2+]i response. Activation
of P2X receptors may modulate the uptake of neurotransmitters from the
extracellular space by Müller cells in the retina.
Key words:
Müller cells; glia; P2 receptors; ATP; glutamate
uptake; human
Copyright © 2000 Society for Neuroscience 0270-6474/00/20165965-08$05.00/0
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