Extracellular chelation of zinc does not affect hippocampal excitability and seizure-induced cell death in rats.
In the nervous system, zinc can influence synaptic responses and at extreme concentrations contributes to epileptic and ischaemic neuronal injury. Zinc can originate from synaptic vesicles, the extracellular space and from intracellular stores. In this study, we aimed to determine which of these zinc pools is responsible for the increased hippocampal excitability observed in zinc-depleted animals or following zinc chelation. Also, we investigated the source of intracellularly accumulating zinc in vulnerable neurons. Our data show that membrane-permeable and membrane-impermeable zinc chelators had little or no effect on seizure activity in the CA3 region. Furthermore, extracellular zinc chelation could not prevent the accumulation of lethal concentrations of zinc in dying neurons following epileptic seizures. At the electron microscopic level, zinc staining significantly increased at the presynaptic membrane of mossy fibre terminals in kainic acid-treated animals. These data indicate that intracellular but not extracellular zinc chelators could influence neuronal excitability and seizure-induced zinc accumulation observed in the cytosol of vulnerable neurons.
Lavoie
Nathalie
N
Centre de Recherche Université Laval Robert Giffard, 2601 chemin de la Canardière, Québec, Canada G1J 2G3.
Peralta
Modesto R
MR
Chiasson
Marilou
M
Lafortune
Kathleen
K
Pellegrini
Luca
L
Seress
László
L
Tóth
Katalin
K
D000818:Animals; D016923:Cell Death; D002614:Chelating Agents / Q000494:pharmacology*; D002712:Chlorides / Q000008:administration & dosage / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D004594:Electrophysiology; D005110:Extracellular Space / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology*; D007276:Injections, Intraventricular; D008297:Male; D008854:Microscopy, Electron; D009410:Nerve Degeneration / Q000503:physiopathology; D009415:Nerve Net / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000378:metabolism / Q000473:pathology*; D013569:Synapses / Q000378:metabolism; D015032:Zinc / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology*; D017967:Zinc Compounds / Q000008:administration & dosage / Q000494:pharmacology
D002614:Chelating Agents; D002712:Chlorides; D017967:Zinc Compounds; C016837:zinc chloride; D004492:Edetic Acid; D015032:Zinc