Potassium-evoked glutamate release liberates arachidonic acid from cortical neurons

Ava L. Taylor, Sandra J. Hewett

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)43881-43887
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number46
DOIs
StatePublished - Nov 15 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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