A role for intracellular zinc in glioma alteration of neuronal chloride equilibrium

S. Di Angelantonio, E. Murana, S. Cocco, F. Scala, C. Bertollini, M. G. Molinari, C. Lauro, P. Bregestovski, C. Limatola, D. Ragozzino

Research output: Contribution to journalArticlepeer-review


Glioma patients commonly suffer from epileptic seizures. However, the mechanisms of glioma-associated epilepsy are far to be completely understood. Using glioma-neurons co-cultures, we found that tumor cells are able to deeply influence neuronal chloride homeostasis, by depolarizing the reversal potential of ?-aminobutyric acid (GABA)-evoked currents (EGABA). EGABA depolarizing shift is due to zinc-dependent reduction of neuronal KCC2 activity and requires glutamate release from glioma cells. Consistently, intracellular zinc loading rapidly depolarizes EGABA in mouse hippocampal neurons, through the Src/Trk pathway and this effect is promptly reverted upon zinc chelation. This study provides a possible molecular mechanism linking glioma invasion to excitation/inhibition imbalance and epileptic seizures, through the zinc-mediated disruption of neuronal chloride homeostasis.

Original languageEnglish
Article numbere1501
JournalCell Death and Disease
Issue number10
Publication statusPublished - Jan 1 2014

ASJC Scopus subject areas

  • Cell Biology
  • Immunology
  • Cancer Research
  • Cellular and Molecular Neuroscience
  • Medicine(all)


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