title: Inhibition of the Na(+)-Ca++ exchanger enhances anoxia and glucopenia-induced [3H]aspartate release in hippocampal slices.
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.
authors.affiliation: Department of Human Communication Sciences, School of Medicine, University of Naples, Federico II, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Amoroso
authors.forename: S
authors.initials: S
authors.lastname: Sensi
authors.forename: G
authors.initials: G
authors.lastname: di Renzo
authors.forename: L
authors.initials: L
authors.lastname: Annunziato
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000187:drug effects / Q000502:physiology*; D015687:Cell Hypoxia; D004533:Egtazic Acid / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency*; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D007811:Lanthanum / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D019831:Sodium-Calcium Exchanger; D001224:Aspartic Acid; D013779:Tetrodotoxin; D004533:Egtazic Acid; D007811:Lanthanum; D000584:Amiloride; D012964:Sodium; D005947:Glucose; D002118:Calcium