Inhibition of the Na+-Ca++ exchanger enhances anoxia and glucopenia- induced [3H]aspartate release in hippocampal slices

S. Amoroso, S. Sensi, G. Di Renzo, L. Annunziato

Research output: Contribution to journalArticle

Abstract

The aim of the present study was to investigate the possible role played by the Na+-Ca++ exchange system in the modulation of D-[3H]aspartate release induced by anoxia and glucopenia from hippocampal slices. When hippocampal slices were exposed to anoxic and glucopenic conditions (oligomycin + 2-deoxyglucose or 95% N2/5% CO2), an increase of basal D- [3H]aspartate release occurred. Two organic calcium entry blockers, verapamil and nimodipine, and the inorganic calcium entry blocker, gadolinium, did not prevent anoxia-induced D-[3H]aspartate release. In contrast, the calcium-chelator, EGTA, and lanthanum, an inorganic compound that blocks voltage-sensitive calcium channels and Na+-Ca++ exchanger activity, enhanced anoxia-induced D-[3H]aspartate release. In addition, the 2'-4'-dimethylbenzil amiloride derivative, a rather specific inhibitor of the Na+-Ca++ exchanger system, enhanced anoxia-induced D-[3H]aspartate release. Finally, tetrodotoxin, which selectively blocks the Na+-channels, attenuated anoxia-elicited D-[3H]aspartate release. In conclusion, the results of the present study confirmed that, under anoxic and glucopenic conditions, D-[3H]aspartate release was not dependent on the entrance of extracellular Ca++ ions through the voltage-sensitive calcium channels and demonstrated that the inhibition of the Na+-Ca++ antiporter enhanced excitatory amino acid release. This result seems to suggest that, when intracellular Na+ concentrations increase, because of the anoxic and glucopenic conditions, both the Na+-Ca++ exchanger and the Na+- syntransporter system of glutamate operate as Na+ ion efflux pathways. Therefore, when the antiporter is blocked, the syntransporter remains the only pathway for Na+ ion extrusion, leading to an enhancement of D- [3H]aspartate release.

Original languageEnglish
Pages (from-to)515-520
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume264
Issue number2
Publication statusPublished - 1994

ASJC Scopus subject areas

  • Pharmacology

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