Modulation of the glutamate-evoked release of arachidonic acid from mouse cortical neurons: Involvement of a pH-sensitive membrane phospholipase A2

Nephi Stella*, Luc Pellerin, Pierre J. Magistretti

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

Excitatory synaptic transmission is associated with changes in both extracellular and intracellular pH. Using mouse cortical neurons in primary cultures, we studied the sensitivity of glutamate-evoked release of 3H- arachidonic acid (3H-AA) to changes in extracellular pH (pH(o)) and related intracellular pH (pH(i)). As pH(o) was shifted from 7.2 to 7.8, the glutamate-evoked release of 3H-AA was enhanced by ~ threefold. The effect of alkaline pH(o) on the glutamate response was rapid, becoming significant within 2 min. 3H-AA release, evoked by both NMDA and kainate, was also enhanced by pH(o) alkalinization. NMDA- and kainate-induced increase in free intracellular Ca2+ was unaffected by changing pH(o) from 7.2 to 7.8, indicating that the receptor-induced Ca2+ influx is not responsible for the pH(o) sensitivity of the glutamate-evoked release of 3H-AA. Alkalinization of pH(i) obtained by incubating neurons in the presence of HCO3 or NH4 enhanced the glutamate-evoked release of 3H-AA, while ph(i) acidification obtained by blockade of Na+/H+ and Cl-/HCO3 exchangers decreased the glutamate response. Membrane-bound phospholipase A2 (mPLA2) activity was stimulated by Ca2+ in a pH-dependent manner, increasing its activity as pH was shifted from 7.2 to 7.8. This pH profile corresponds to the pH profile of the glutamate-, NMDA- and kainate-evoked release of 3H-AA. Taken together, these results indicate that the glutamate-evoked release of 3H-AA may be mediated by the pH-sensitive mPLA2. Since excitatory neurotransmission mediated by glutamate results in both pH(o) and pH(i) changes and since AA enhances glutamatergic neurotransmission at both pre- and postsynaptic levels, the data reported here reveals a possible molecular mechanism whereby glutamate can modulate its own signalling efficacy in a pH-dependent manner by regulating the release of AA.

Original languageEnglish (US)
Pages (from-to)3307-3317
Number of pages11
JournalJournal of Neuroscience
Volume15
Issue number5 I
DOIs
StatePublished - May 1995

Keywords

  • H
  • NMDA
  • intracellular Ca
  • ischemia
  • kainate
  • long-term potentiation

ASJC Scopus subject areas

  • Neuroscience(all)

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