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The Journal of Neuroscience, March 1, 2003, 23(5):1659

Glial Cell Inhibition of Neurons by Release of ATP

Eric A. Newman

Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455

ATP is released by neurons and functions as a neurotransmitter and modulator in the CNS. Here I show that ATP released from glial cells can also serve as a potent neuromodulator, inhibiting neurons in the retina of the rat. Activation of glial cells by focal ejection of ATP, ATPS, dopamine, thrombin, or lysophosphatidic acid or by mechanical stimulation evoked hyperpolarizing responses and outward currents in a subset of retinal ganglion cells by increasing a Ba²⁺-sensitive K⁺ conductance in the neurons. This glia-evoked inhibition reduced the firing rate of those neurons that displayed spontaneous spike activity. The inhibition was abolished by the A₁ adenosine receptor antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine) (10 nM) and was reduced by the ecto-ATPase inhibitor ARL-67156 (6-N,N-diethyl-D-,-dibromomethyleneATP) (50 µM) and by the ectonucleotidase inhibitor AOPCP [adenosine-5'-O-(,-methylene)-diphosphonate] (250 µM). Selective activation of retinal glial cells demonstrated that Müller cells, but not astrocytes, mediate the inhibition. ATP release from Müller cells into the inner plexiform layer of the retina was shown using the luciferin-luciferase chemiluminescence assay. These findings demonstrate that activated glial cells can inhibit neurons in the retina by the release of ATP, which is converted to adenosine by ectoenzymes and subsequently activates neuronal adenosine receptors. The results lend support to the hypothesis that glial cells play an active role in information processing in the CNS.

Key words: astrocyte; Müller cell; glial cell; ganglion cell; retina; ATP; adenosine; modulation; inhibition

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Copyright © 2003 Society for Neuroscience  0270-6474/03/2351659-08$05.00/0

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