PT  - JOURNAL ARTICLE
AU  - John W. McDonald
AU  - Tim Bhattacharyya
AU  - Stefano L. Sensi
AU  - Doug Lobner
AU  - Howard S. Ying
AU  - Lorella M.T. Canzoniero
AU  - Dennis W. Choi
TI  - Extracellular Acidity Potentiates AMPA Receptor-Mediated Cortical Neuronal Death
AID  - 10.1523/JNEUROSCI.18-16-06290.1998
DP  - 1998 Aug 15
TA  - The Journal of Neuroscience
PG  - 6290--6299
VI  - 18
IP  - 16
4099  - http://www.jneurosci.org/content/18/16/6290.short
4100  - http://www.jneurosci.org/content/18/16/6290.full
SO  - J. Neurosci.1998 Aug 15; 18
AB  - 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.