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Am J Physiol Cell Physiol (April 18, 2002). doi:10.1152/ajpcell.00438.2001
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Articles in PresS, published online ahead of print April 18, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00438.2001
Submitted on September 11, 2001
Accepted on April 9, 2002

ATP potently modulates anion channel-mediated excitatory amino acid release from cultured astrocytes

Alexander A. Mongin1 and Harold K. Kimelberg1*

1 Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, NY, USA

* To whom correspondence should be addressed. E-mail: kimelbh{at}mail.amc.edu.

Volume-dependent ATP release and subsequent activation of purinergic P2Y receptors have been implicated as an autocrine mechanism triggering activation of volume-regulated anion channels (VRACs) in hepatoma cells. In the CNS ATP is released by both neurons and astrocytes and participates in intercellular communication. In the present work we explored whether ATP triggers or modulates the release of excitatory amino acid (EAAs) via VRACs in astrocytes in primary culture. Under basal conditions exogenous ATP (10 µM) activated a small EAA release in 70-80% of the cultures tested. In both moderately swollen (5% reduction of medium osmolarity) and substantially swollen (35% reduction of medium osmolarity) astrocytes, exogenous ATP greatly potentiated EAA release. The effects of ATP were mimicked by P2Y agonists and eliminated by P2Y antagonists or the ATP scavenger apyrase. In contrast, the same pharmacological maneuvers did not inhibit volume-dependent EAA release in the absence of exogenous ATP, ruling out a requirement of autocrine ATP release for VRAC activation. The ATP effect in non-swollen and moderately swollen cells was eliminated by a 5-10% increase in medium osmolarity or by anion channel blockers, but was insensitive to tetanus toxin pretreatment, further supporting VRAC involvement. Our data suggest that in astrocytes ATP does not trigger EAA release itself but acts synergistically with cell swelling. Moderate cell swelling and ATP may serve as two cooperative signals in bi-directional neuron-astrocyte communication in vivo.




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