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

Fingerprint

D-Aspartic Acid
Aspartic Acid
Antiporters
Calcium Channels
Ions
Calcium
Oligomycins
Lanthanum
Nimodipine
Excitatory Amino Acids
Hypoxia
Amiloride
Egtazic Acid
Tetrodotoxin
Deoxyglucose
Gadolinium
Verapamil
Glutamic Acid

ASJC Scopus subject areas

  • Pharmacology

Cite this

Inhibition of the Na+-Ca++ exchanger enhances anoxia and glucopenia- induced [3H]aspartate release in hippocampal slices. / Amoroso, S.; Sensi, S.; Di Renzo, G.; Annunziato, L.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 264, No. 2, 1994, p. 515-520.

Research output: Contribution to journalArticle

@article{f42331ea2dcf45bf8303eefa65e58520,
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.",
author = "S. Amoroso and S. Sensi and {Di Renzo}, G. and L. Annunziato",
year = "1994",
language = "English",
volume = "264",
pages = "515--520",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "2",

}

TY - JOUR

T1 - Inhibition of the Na+-Ca++ exchanger enhances anoxia and glucopenia- induced [3H]aspartate release in hippocampal slices

AU - Amoroso, S.

AU - Sensi, S.

AU - Di Renzo, G.

AU - Annunziato, L.

PY - 1994

Y1 - 1994

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0028142552&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028142552&partnerID=8YFLogxK

M3 - Article

C2 - 8437103

AN - SCOPUS:0028142552

VL - 264

SP - 515

EP - 520

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 2

ER -