Potassium-evoked glutamate release liberates arachidonic acid from cortical neurons

Ava L. Taylor, Sandra J. Hewett

Research output: Contribution to journalArticlepeer-review

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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