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J. Biol. Chem., Vol. 277, Issue 46, 43881-43887, November 15, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/46/43881    most recent M205872200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Taylor, A. L. Articles by Hewett, S. J. Search for Related Content PubMed PubMed Citation Articles by Taylor, A. L. Articles by Hewett, S. J. Social Bookmarking                      What's this?

Potassium-evoked Glutamate Release Liberates Arachidonic Acid from Cortical Neurons^*

Ava L. Taylor and Sandra J. Hewett

From the Department of Neuroscience, University of Connecticut School of Medicine, Farmington, Connecticut 06030-3401

Brain cells in situ contain low concentrations of free polyunsaturated fatty acids such as arachidonic acid (AA) that are released following pathological insults. As a large rise in extracellular [K⁺] accompanies cerebral ischemia, we explored whether this was a stimulus for cellular AA release employing a murine mixed cortical cell culture preparation radiolabeled with AA. Elevating the [K⁺]_o from 5 to 52 mM induced a time-dependent increase in [³H]AA release, which reached a plateau after 15 min. Removal of [Ca²⁺]_o or addition of CdCl₂ (100 µM) diminished the net high K⁺-induced AA release, as did treatment of the cultures with tetanus toxin (300 ng/ml) to block endogenous neurotransmitter release. Pharmacological antagonism of both ionotropic and metabotropic glutamate receptors completely prevented high K⁺-evoked AA release, indicating that glutamate was the neurotransmitter in question. Addition of exogenous glutamate mimicked precisely the characteristics of AA release that followed increases in [K⁺]_o. Finally, glutamate and AA were released solely from neurons as tetanus toxin did not cleave astrocytic synaptobrevin-2, nor was AA released from pure astrocyte cultures using the same stimuli that were effective in mixed cultures. Taken in toto, our data are consistent with the following scenario: high [K⁺]_o depolarizes neurons, causing an influx of Ca²⁺ via voltage-gated Ca²⁺ channels. This Ca²⁺ influx stimulates the release of glutamate into the synaptic cleft, where it activates postsynaptic glutamate receptors. Events likely converge on the activation of a phospholipase A₂ family member and possibly the enzymes diacylglycerol and monoacylglycerol lipases to yield free AA.

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