Title
Loss of synaptic <tex>$Zn^{2+}$</tex> transporter function increases risk of febrile seizures Loss of synaptic <tex>$Zn^{2+}$</tex> transporter function increases risk of febrile seizures
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
London :Nature Publishing Group ,
Subject
Engineering sciences. Technology
Source (journal)
Scientific reports. - London, 2011, currens
Volume/pages
5(2015) , 9 p.
ISSN
2045-2322
2045-2322
Article Reference
17816
Carrier
E-only publicatie
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Febrile seizures (FS) are the most common seizure syndrome and are potentially a prelude to more severe epilepsy. Although zinc (Zn2+) metabolism has previously been implicated in FS, whether or not variation in proteins essential for Zn2+ homeostasis contributes to susceptibility is unknown. Synaptic Zn2+ is co-released with glutamate and modulates neuronal excitability. SLC30A3 encodes the zinc transporter 3 (ZNT3), which is primarily responsible for moving Zn2+ into synaptic vesicles. Here we sequenced SLC30A3 and discovered a rare variant (c.892C > T; p.R298C) enriched in FS populations but absent in population-matched controls. Functional analysis revealed a significant loss-of-function of the mutated protein resulting from a trafficking deficit. Furthermore, mice null for ZnT3 were more sensitive than wild-type to hyperthermia-induced seizures that model FS. Together our data suggest that reduced synaptic Zn2+ increases the risk of FS and more broadly support the idea that impaired synaptic Zn2+ homeostasis can contribute to neuronal hyperexcitability.
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Full text (open access)
https://repository.uantwerpen.be/docman/irua/00c0b9/130215.pdf
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