Extracellular Acidity Potentiates AMPA Receptor-mediated Cortical Neuronal Death

Overview

Journal J Neurosci

Specialty Neurology

Date 1998 Aug 11

PMID 9698321

Citations 18

Authors

J W McDonald

T Bhattacharyya

S L Sensi

D Lobner

H S Ying

L M Canzoniero

D W Choi

Affiliations

Soon will be listed here.

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.

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