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

S Di Angelantonio (1, 2) , E Murana (1) , S Cocco (1) , F Scala (1) , C Bertollini (1) , M G Molinari (1) , C Lauro (1) , P Bregestovski (3) , C Limatola (1, 4) , D Ragozzino (1, 4)

1 Department of Physiology and Pharmacology
2 Center for Life Nano Science at Sapienza
3 INS - Institut de Neurosciences des Systèmes
4 NEUROMED I.R.C.C.S. - Istituto Neurologico Mediterraneo

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 γ-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.

Domaines: Neurosciences [q-bio.NC]

S Di Angelantonio, E Murana, S Cocco, F Scala, C Bertollini, et al.. A role for intracellular zinc in glioma alteration of neuronal chloride equilibrium.. Cell Death and Disease, 2014, 5, pp.e1501. ⟨10.1038/cddis.2014.437⟩. ⟨pasteur-01182336⟩