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 journalArticle

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
StatePublished - Aug 15 1998
Externally publishedYes

Fingerprint

Kainic Acid Receptors
AMPA Receptors
N-Methyl-D-Aspartate Receptors
Brain Hypoxia-Ischemia
N-Methylaspartate
Homeostasis
Ischemia
Cell Culture Techniques
Wounds and Injuries

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

McDonald, J. W., Bhattacharyya, T., Sensi, S. L., Lobner, D., Ying, H. S., Canzoniero, L. M. T., & Choi, D. W. (1998). Extracellular acidity potentiates AMPA receptor-mediated cortical neuronal death. Journal of Neuroscience, 18(16), 6290-6299.

Extracellular acidity potentiates AMPA receptor-mediated cortical neuronal death. / McDonald, John W.; Bhattacharyya, Tim; Sensi, Stefano L.; Lobner, Doug; Ying, Howard S.; Canzoniero, Lorella M T; Choi, Dennis W.

In: Journal of Neuroscience, Vol. 18, No. 16, 15.08.1998, p. 6290-6299.

Research output: Contribution to journalArticle

McDonald, JW, Bhattacharyya, T, Sensi, SL, Lobner, D, Ying, HS, Canzoniero, LMT & Choi, DW 1998, 'Extracellular acidity potentiates AMPA receptor-mediated cortical neuronal death', Journal of Neuroscience, vol. 18, no. 16, pp. 6290-6299.
McDonald JW, Bhattacharyya T, Sensi SL, Lobner D, Ying HS, Canzoniero LMT et al. Extracellular acidity potentiates AMPA receptor-mediated cortical neuronal death. Journal of Neuroscience. 1998 Aug 15;18(16):6290-6299.
McDonald, John W. ; Bhattacharyya, Tim ; Sensi, Stefano L. ; Lobner, Doug ; Ying, Howard S. ; Canzoniero, Lorella M T ; Choi, Dennis W. / Extracellular acidity potentiates AMPA receptor-mediated cortical neuronal death. In: Journal of Neuroscience. 1998 ; Vol. 18, No. 16. pp. 6290-6299.
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