Extracellular acidity potentiates AMPA receptor-mediated cortical neuronal death

John W. McDonald, Tim Bhattacharyya, Stefano L. Sensi, Doug Lobner, Howard S. Ying, Lorella M.T. Canzoniero, Dennis W. Choi

Research output: Contribution to journalArticlepeer-review

Abstract

The extracellular acidity that accompanies brain hypoxia-ischemia is known to reduce both NMDA and AMPA-kainate receptor-mediated currents and NMDA receptor-mediated neurotoxicity. Although a protective effect of acidic pH on AMPA-kainate receptor-mediated excitotoxicity has been assumed, such has not been demonstrated. Paradoxically, we found that lowering extracellular pH selectively increased AMPA-kainate receptor-mediated neurotoxicity in neocortical cell cultures, despite reducing peak elevations in intracellular free Ca2+. This injury potentiation may, at least in part, be related to a slowed recovery of intracellular Ca2+ homeostasis, observed after AMPA-kainate receptor activation, but not after NMDA receptor activation or exposure to high K+. The ability of acidic pH to selectively augment AMPA-kainate receptor-mediated excitotoxicity may contribute to the prominent role that these receptors play in selective neuronal death after transient global ischemia.

Original languageEnglish (US)
Pages (from-to)6290-6299
Number of pages10
JournalJournal of Neuroscience
Volume18
Issue number16
DOIs
StatePublished - Aug 15 1998

Keywords

  • AMPA
  • Acidosis
  • Cyclothiazide
  • Excitotoxicity
  • Murine neuronal culture
  • PH

ASJC Scopus subject areas

  • Neuroscience(all)

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