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Arachidonic acid induces a prolonged inhibition of glutamate uptake into glial cells

Nature volume 342, pages 918–920 (1989)Cite this article

Abstract

ACTIVATION of NMDA (N-methyl-D-aspartate) receptors by neurotransmitter glutamate stimulates phospholipase A2 to release arachidonic acid1,2. This second messenger facilitates long-term potentiation of glutamatergic synapses in the hippocampus3, possibly by blocking glutamate uptake4,5. We have studied the effect of arachidonic acid on glutamate uptake into glial cells using the whole-cell patch-clamp technique to monitor the uptake electrically6,7. Micromolar levels of arachidonic acid inhibit glutamate uptake, mainly by reducing the maximum uptake rate with only small effects on the affinity for external glutamate and sodium. On removal of arachidonic acid a rapid (5 minutes) phase of partial recovery is followed by a maintained suppression of uptake lasting at least 20 minutes. Surprisingly, the action of arachidonic acid is unaffected by cyclo-oxygenase or lipoxygenase inhibitors suggesting that it inhibits uptake directly, possibly by increasing membrane fluidity. As blockade of phospholipase A2 prevents the induction of long-term potentiation (LTP) 8, inhibition of glutamate uptake by arachidonic acid may contribute to the increase of synaptic gain that occurs in LTP. During anoxia, release of arachidonic acid9 could severely compromise glutamate uptake and thus contribute to neuronal death.

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Authors and Affiliations

  1. Department of Physiology, University College London, Gower Street, London, WC1E 6BT, UK

    Boris Barbour, Marek Szatkowski, Nick Ingledew & David Attwell

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Barbour, B., Szatkowski, M., Ingledew, N. et al. Arachidonic acid induces a prolonged inhibition of glutamate uptake into glial cells. Nature 342, 918–920 (1989). https://doi.org/10.1038/342918a0

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