Pharmacological evidence that the activation of the Na +-Ca 2+ exchanger protects C6 glioma cells during chemical hypoxia

Salvatore Amoroso, Matteo De Maio, Giovanni M. Russo, Annalisa Catalano, Antonella Bassi, Stefania Montagnani, Gianfranco Di Renzo, Lucio Annunziato

Research output: Contribution to journalArticlepeer-review

Abstract

1. In C6 glioma cells exposed to chemical hypoxia a massive release of lactate dehydrogenase (LDH) occurred at 3 and 6 h, coupled with an increased number of propidium-iodide positive dead cells. 2. Extracellular Na + removal, which activates the Na +-Ca 2+ exchanger as a Na + efflux pathway and prevents Na + entrance, significantly reduced LDH release and the number of propidium iodide positive C6 cells. 3. During chemical hypoxia, in the presence of extracellular Na + ions, a progressive increase of [Ca 2+](i) occurred; in the absence of extracellular Na + ions [Ca 2+](i) was enhanced to a greater extent. 4. The blockade of the Na +-Ca 2+ exchanger by the amiloride derivative 5-(N-4-chlorobenzyl)-2',4'-dimethylbenzamil (CB-DMB), lanthanum (La 3+) and the Ca 2+ chelator EGTA, completely reverted the protective effect exerted by the removal of Na + ions on C6 glioma cells exposed to chemical hypoxia. 5. The inhibition of the Na +-Ca 2+ antiporter enhanced chemical hypoxia-induced LDH release when C6 glioma cells were incubated in the presence of physiological concentrations of extracellular Na + ions (145 mM), suggesting that the blockade of the Na +-Ca 2+ antiporter during chemical hypoxia can lead to increased cell damage. 6. Collectively, these results suggest that activation of the Na +-Ca 2+ exchanger protects C6 glioma cells exposed to chemical hypoxia, whereas its pharmacological blockade can exacerbate cellular injury.

Original languageEnglish
Pages (from-to)303-309
Number of pages7
JournalBritish Journal of Pharmacology
Volume121
Issue number2
Publication statusPublished - 1997

Keywords

  • Amiloride analogue
  • C6 glioma cells
  • Chemical hypoxia
  • Na -Ca exchanger

ASJC Scopus subject areas

  • Pharmacology

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